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Background: All living organisms are made of individual and identifiable cells, whose number, together with their size and type, ultimately defines the structure and functions of an organism. While the total cell number of lower organisms is often known, it has not yet been defined in higher organisms. In particular, the reported total cell number of a human being ranges between 10(12) and 10(16) and it is widely mentioned without a proper reference. Aim: To study and discuss the theoretical issue of the total number of cells that compose the standard human adult organism. Subjects and methods: A systematic calculation of the total cell number of the whole human body and of the single organs was carried out using bibliographical and/or mathematical approaches. Results: A current estimation of human total cell number calculated for a variety of organs and cell types is presented. These partial data correspond to a total number of 3.72 × 10(13). Conclusions: Knowing the total cell number of the human body as well as of individual organs is important from a cultural, biological, medical and comparative modelling point of view. The presented cell count could be a starting point for a common effort to complete the total calculation.
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2013
http://informahealthcare.com/ahb
ISSN: 0301-4460 (print), 1464-5033 (electronic)
Ann Hum Biol, Early Online: 1–11
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2013 Informa UK Ltd. DOI: 10.3109/03014460.2013.807878
ORIGINAL ARTICLE
An estimation of the number of cells in the human body
Eva Bianconi
1
, Allison Piovesan
1
, Federica Facchin
1
, Alina Beraudi
2
, Raffaella Casadei
3
, Flavia Frabetti
1
,
Lorenza Vitale
1
, Maria Chiara Pelleri
1
, Simone Tassani
4
, Francesco Piva
5
, Soledad Perez-Amodio
6
, Pierluigi Strippoli
1
,
and Silvia Canaider
1
1
Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy,
2
Medical Technology Lab, Prometeo Lab
(RIT), Istituto Ortopedico Rizzoli, Bologna, Italy,
3
Department for Life Quality Studies, University of Bologna, Rimini, Italy,
4
Institute of
Communication and Computer Systems, Athens, Greece,
5
Department of Specialized Clinical Sciences and Odontostomatology, School of Medicine,
Polytechnic University of Marche, Ancona, Italy, and
6
Biomaterials for Regenerative Therapies Group, Institute for Bioengineering of Catalunya
(IBEC), Barcelona, Spain
Abstract
Background: All living organisms are made of individual and identifiable cells, whose number,
together with their size and type, ultimately defines the structure and functions of an organism.
While the total cell number of lower organisms is often known, it has not yet been defined in
higher organisms. In particular, the reported total cell number of a human being ranges
between 10
12
and 10
16
and it is widely mentioned without a proper reference.
Aim: To study and discuss the theoretical issue of the total number of cells that compose the
standard human adult organism.
Subjects and methods: A systematic calculation of the total cell number of the whole human
body and of the single organs was carried out using bibliographical and/or mathematical
approaches.
Results: A current estimation of human total cell number calculated for a variety of organs and
cell types is presented. These partial data correspond to a total number of 3.72 10
13
.
Conclusions: Knowing the total cell number of the human body as well as of individual organs is
important from a cultural, biological, medical and comparative modelling point of view. The
presented cell count could be a starting point for a common effort to complete the total
calculation.
Keywords
Cell size, human cell number, organ, total cell
count, theoretical issue
History
Received 26 September 2012
Revised 19 March 2013
Accepted 9 May 2013
Published online 5 July 2013
Introduction
Since Schleidens and Schwann’s first formulations of cell
theory (Mazzarello, 1999), it has been known that all living
organisms are made of individual and identifiable cells,
whose size, number and type ultimately define the structure,
functions and size of an organism.
Cell size appears to be regulated by the amount of DNA
(ploidy): for example, the diploid yeast is larger than the
haploid one (Su & O’Farrell, 1998); cells in a tetraploid
salamander are twice the size of those in a diploid salaman-
der, although the corresponding organs in the two animals
have the same size, because the organisms of the tetraploid
salamander contain half as many cells as those of the diploid
(Conlon & Raff, 1999). Nevertheless, the issue of what kind
of relationship or signalling there is between cell size and
DNA content is still unresolved. It has been hypothesized that
there is a maximal protein-production rate from a genome
because there is an upper limit to gene transcription and
translation rates. Since proteins have a limited lifetime, there
is a maximal amount of protein-associated cell mass that can
be supported by a genome (Gomer, 2001). In size-control
mechanisms, even cell communication has a role in defining
specific organs, as reported by Depaepe et al. (2005).
Cell number, on the other hand, appears to be under strict
genetic and developmental control in lower organisms: for
example, bacteria and yeasts are composed of single cells,
while the adult Caenorhabditis elegans worm consists of
exactly 959 (male) or 1031 (ermaphrodite) somatic cells
(Alberts et al., 2002). In contrast, how cell number is
determined in higher organisms is not understood, although it
is presumably regulated by wider mechanisms of homeostasis
such as proliferation, differentiation and cell death. According
to this, Notch signalling can prolong precursor cell division
and can maintain stem cells in a self-renewing pattern of
division, thereby indirectly increasing the number of differ-
entiated cells that are ultimately produced (Conlon & Raff,
1999). There are currently several examples of secreted
factors that regulate tissue size, by both increasing and
limiting proliferation. Examples are myostatin, which regu-
lates skeletal muscle mass; leptin, which regulates the amount
of adipose tissue; growth hormone and insulin-like growth
Correspondence: Pierluigi Strippoli, Department of Experimental,
Diagnostic and Specialty Medicine, University of Bologna, Bologna,
Italy. Tel: +39 051 2094100. Fax: +39 051 2094110. E-mail:
pierluigi.strippoli@unibo.it
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factors, which regulate total body mass (Roisin-Bouffay &
Gomer, 2004), and Hh-Gli signalling factors, which play a
central role in controlling precursor cell numbers in the brain
and other organs (Stecca & Ruiz i Altaba, 2009).
Some factors, such as insulin-signalling pathway, are
central in controlling cell number and size from worms to
humans, supporting the idea that key functions of the pathway
have been powerfully conserved through evolution (Moore,
2003). However, it has also been suggested that there may be
fundamental differences in the mechanisms by which mam-
mals and insects control their body size. This is the case
of c-myc, indicated as a crucial signal mediator: in mice its
reduction resulted in multi-organ hypoplasia, while
Drosophila c-myc mutants were found to be smaller because
of hypotrophy (Trumpp et al., 2001).
In complex organisms, composed of many billions of cells,
it is expected that control of cell number does not reach
precision at the level of single cells. However, at least a
defined order of magnitude in body cell number should be
conserved among humans, on the basis of several consider-
ations. First, although there are obvious differences in body
height and mass among adult individuals, these variations are
not greater than one order of magnitude and they may be due
to an increase in cell size along with or in absence of an
increase in cell number, such as in obesity (Avram et al.,
2007; Salans et al., 1973). In addition, analysis of cell number
at single organ or tissue level shows a considerable degree of
conservation among human organisms, i.e. blood cells count.
Biological experimental data point to an ‘‘organ-size check-
point’’ that generates organs of reproducible shape and size in
metazoans by regulating cell division, cell growth and
apoptosis, involving genes regulating patterning or controlling
cell adhesion and cell polarity (Leevers & McNeill, 2005).
Finally, consistency of basic molecular and cellular mechan-
isms for the development of an initial single cell (zygote) into
a complete organism with a reproducible anatomy and
physiology and conservation of these mechanisms through
evolution, suggest that a fine control of cell number is
exerted at genetic level in a similar manner for all individuals
of a certain species. In fact, there are clear physical
constraints on upper and lower limits of organism and organ
size, such as bone or heart mechanics and surface-to-volume
ratio, and biological mechanisms aimed at controlling
body and tissue cell number (Gomer, 2001; Hafen &
Stocker, 2003).
The aim of this work is to discuss the theoretical issue of
the total number of cells that compose the standard human
adult organism.
First, we noticed that these data were typically mentioned
in the literature without citing a reference; second, we
observed wide ranges among data reported by different
sources, ranging from 10
12
–10
20
.
We followed different lines of research in order to:
undertake a systematic survey of available information
about the number of cells of a human organism known to
date; assess this number using rough estimations for the body
as a whole; provide a framework and accurate count of
specific organs or cell types. In addition, we discuss the
relevance of this topic with regard to its applications in
biology and medicine, the complexity of deriving the total
cell number and, finally, we launch an international open
debate aimed at a final and documented solution of the
problem.
Materials and methods
Different approaches were used to retrieve all data available
to date on the total human cell number for a human being
or for a specific system/organ or cell type. Moreover, we
obtained useful data from the literature in order to calculate
the total cell number of specific system/organ or cell types
not yet known. Since the cell number and cell size of
various organs or systems, as well as the size of the organ
or system itself, may vary according to several parameters
such as age, sex, weight, pathology or evolutionary
adaptations, we searched for a single reference for the
‘‘average man’’ or ‘‘standard human being’’. Since this
does not exist, for the purposes of this work we chose a
30-year old young adult, weighing 70 kg, 1.72 m tall and
with a body area of 1.85 m
2
(Irving, 2007). When retrieved
data were different from this ‘‘average man’’ this was
indicated in the specific section.
Bibliographical search
In order to find primary literature articles with information
about the cell number of a human organism, we systematically
searched the PubMed database (http://www.ncbi.nlm.nih.gov/
pubmed/). Searching for the MeSH term ‘‘Cell Count’’,
corresponding to ‘‘cell number’’, led to non-specific results
(more than 168 000 items found). The PubMed search was
therefore adjusted by using MeSH sub-headings and by
restricting results to Homo sapiens. The search was performed
using the expression: (‘‘Cell Count’’[Mesh] OR ‘‘cell
number’’) AND (‘‘Body Weights and Measures’’[Mesh] OR
‘‘Body Size’’[Mesh] OR ‘‘Body Constitution’’[Mesh] OR
‘‘Body Composition’’[Mesh]) AND ‘‘Humans’’[Mesh] AND
(1809[PDAT]: 2012/01/31[PDAT]). In addition, a search
including the explicit expression ‘‘cell number’’ along with
the terms ‘‘body’’ or ‘‘organism’’, limited to humans but not
including the MeSH sub-headings used above, was performed
in the title/abstract fields of PubMed. In this case the PubMed
query was: (Human[Title/Abstract] OR ‘‘Humans’’[Mesh])
AND (body[Title/Abstract] OR organism[Title/Abstract])
AND ‘‘cell number’’[Title/Abstract] AND (1809[PDAT]:
2012/01/31[PDAT]). Finally, a further search, not including
restriction to the presence of ‘‘body’’ or ‘‘organism’’ terms and
directed to the presence of the expression ‘‘cell number’’ in the
item title was performed by the query: ‘‘Cell number’’[TI]
AND human AND (1809[PDAT]: 2012/01/31[PDAT]).
At the same time, we performed a specific search of the
PubMed database with the purpose of finding primary
literature articles with information on how to calculate the
total cell number of a specific system/organ or cell type not
yet known.
The publication date of the articles searched ranged from
1809 to January 2012. Moreover, we reviewed printed
versions of available texts covering Biology, Genetics,
Histology, Anatomy, Physiology and other potentially useful
available printed sources. In addition, we searched for this
information in the main repositories of electronic versions of
2 E. Bianconi et al. Ann Hum Biol, Early Online: 1–11
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books, NCBI Books (http://www.ncbi.nlm.nih.gov/sites/
entrez?db ¼ books) as well as of Google Books (http://
books.google.com/books), in their versions available up to
January 2012.
The NCBI Books collection includes many reference
textbooks widely used in the biomedical field. It was queried
using a general expression formulated according to the NCBI
Entrez query language: (‘‘Human body’’ OR ‘‘Human organ-
ism’’) AND (Cells OR ‘‘Cell number’’) or a specific request.
The Google Books collection includes books on any
subject whose text has been freely made totally or partially
available. It was searched by using the expression: (‘‘Human
body’’ OR ‘‘Human organism’’) (Cells OR ‘‘Cell number’’)
or a specific request.
The internet search engine Google was searched using
the expression: (‘‘Human body’’ OR ‘‘Human organism’’)
AND (Cells OR ‘‘Cell number’’) or a specific request.
Morphological estimation
It was possible to calculate cell volumes using an ultramicro-
scopic cell or an organ picture by the ‘‘solid revolution
method’’. First, we filtered the pictures in which the scale bar
was reported, the cell/organ was well magnified and its edge
was cleaned.
We plotted the Cartesian axes on the cell/organ picture so
that the axes origin was on the cell edge, the cell lay on the
positive abscissa and this axis split the cell into two identical
parts. We then traced bars with equal base size and
intersecting cell/organ edge in the middle of their top side
(Figure 1); the bars were built so that the sum of their areas
was, as much as possible, equal to the area of the cell/organ
contained in the first quadrant of the Cartesian axes.
An approximation of the cell/organ volume was obtained
by the following formula:
V
approx
¼
X
n
i¼1
f ðx
i
Þ
2
Dx
In order to attain a better approximation of the cell/organ
volume, we chose to sample the function f(x), that represents
the cell/organ edge, in the middle of each interval Dx.
Moreover we sub-divided the abscissa axis (the ‘‘a’’ segment
in Figure 1) laid upon the shape into n equal parts, each with
length . Finally, we re-scaled the cell/organ volume in cubic
micrometres.
Mathematical calculations
Most of the time, data obtained by previous described methods
required mathematical elaborations to find the total cell
number of a human being or the specific system/organ or a
cell type searched. Every time more than one datum was given,
the mean value and the corresponding errors (standard
deviation, SD) were reported alongside the value together
with the corresponding reference that reports them.
Furthermore, when cell size was necessary to perform the
calculation, we declared it in the organ-specific results section.
Moreover, a gross estimation of the total human cell
number was obtained by dividing the mass or volume of a
reference adult human body by the mass or volume,
respectively, of an average human cell.
Results
Estimation of the human total cell number in the
literature
We optimized the PubMed search in order to obtain useful
information about the composition of the human body in
terms of cell number.
The search strategies in PubMed database described in the
‘‘Bibliographical search’’ section led us to retrieve 3407
articles. However, only two articles addressing the specific
issue of the global cell number in the human body were found
(see ‘‘Original article’’ in Appendix A, Table A1).
Searches in printed books, in online NCBI and Google
Books gave useful estimations of total cell number in the
human body (see ‘‘Printed book’’ and ‘‘Online book’’ in
Appendix A, Table A1).
None of these values were justified by primary literature
data and no citation source was available. Many websites
retrieved via Google search reported estimations for the
human whole body cell number. Due to criteria used by the
Google search engine, we consulted the first 100 results,
which led to estimations ranging from 5 10
12
to 7 10
16
,
with a single site reporting 2 10
20
.
Excluding the results without an available primary source,
the estimation of the total human cell number, supported
by a bibliographical reference, ranges from 10
12
–10
16
,
with a modal value of 10
13
(see Figure 2 and Table A1 in
Appendix A).
Gross estimation of the human total cell number by
mass and by volume
Although high variability in the size and weight of cells
from different normal tissues makes it difficult to choose
a reference for human cell weight and volume average
values, we assumed that a global compensation among body
regions exists.
Figure 1. Schematic representation of the cell image position in the
Cartesian axes. It was possible to calculate the cell volume by the ‘‘solid
revolution method’’ approximated by the summation formula, using an
ultramicroscope cell picture. In particular, Cartesian axes have to be
drawn on the cell image so that the x-axis is a symmetrical axis of the
cell, the upper half of the cell (represented by the curve line in the figure)
lies in the first quadrant and the cell edge intersects the origin of the
axes. Bars of identical width have to be drawn in the cell area included
between the cell edge and the x-axis, intersecting the cell edge in the
middle of their top side. In this manner the sum of the areas of all the
bars will approximate the area of this cell portion, while the cell volume
is obtained by measuring each bar height and inserting it in the
summation formula (see details in the ‘‘Morphological estimation’’
section).
DOI: 10.3109/03014460.2013.807878 Human cell number 3
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Therefore, since the mean weight of a mammalian cell has
been estimated to be 1 ng (Makarieva et al., 2008), for a
standard body weight of 70 kg (Irving, 2007), there would be
7 10
13
cells.
The mean volume of a mammalian cell has been estimated
to be 4 10
9
cm
3
(Alberts et al., 2002) (i.e. 4 pL). The
human body mean volume has been calculated by Nagao et al.
(1995) by two different physical methods: the obtained values
were 63.83 and 66.61 L. Considering the average value, the
resulting cell number is 1.63 10
13
cells. Moreover, con-
sidering the body volume indicated by Irving (2007), equal to
60 10
3
cm
3
, the total human cell number resulted to be
1.50 10
13
(Figure 2). However, if a single, 90 fL volume,
blood red cell were to be considered (Tønnesen et al., 1986),
this would translate into a larger number of total cells,
7.24 10
14
.
On the other hand, the estimation of a mean volume of
6 pL for each endothelial cell and of a total number of
35 10
12
human endothelial cells (Genest et al., 1983) would
result in an over-estimated body volume of 210 L.
Estimation of total cell number of specific systems,
organs or cell types
We present here results on the cell number of specific
systems, organs or cell types obtained to date with our
research.
Some of the values regarding the cell number of whole
human organs or cell type were obtained directly from an in-
depth bibliographical search. Other data on total cell number
of whole human organs or cell type needed integration
of some or all methods described above. We report below
these methods and results together for each of them (see
Appendix B, Table B1).
Articular cartilages: Femoral condylar, humeral head
and trochlear surface of talus cartilage total cell
number
Articular cartilage cell number was calculated for some main
joints: the femoral condylar cartilage, the shoulder (humeral
head) and the ankle (trochlear surface of talus). Femoral,
humeral head and talus cartilage volumes have been reported
at 2503 568 mm
3
(lateral femur cartilage), 2770 536 mm
3
(medial femur cartilage) (Baysal et al., 2004),
4200 mm
3
1120 (Vanwanseele et al., 2004) and
3320 550 mm
3
(Millington et al., 2007), respectively.
Femoral, humeral head and talus cartilage cell densities
have been reported at 14 100 3200 cells/mm
3
, 14 600 cells/
mm
3
and 12 150 cells/mm
3
(Stockwell, 1971), respectively.
Based on these data, the calculated cell numbers of two
femoral condyles, two humeral heads and two talus cartilages
were 1.49 0.46 10
8
, 1.23 0.35 10
8
, 8.06 1.56 10
7
,
respectively.
Biliary system: Gallbladder and biliary ducts
epithelium total cell number
The biliary system is composed of the gallbladder and biliary
ducts (Borley, 2005a).
We calculated the gallbladder internal surface (47.03 cm
2
),
by gallbladder internal volume (Irving, 2007) and size
(Borley, 2005a) assuming that it has a prolate spheroidal
shape. By dividing the estimated surface by the single cell
basal surface (29.20 4.21 mm
2
), attained by morphological
estimation (as described in the Methods section) from an
epithelium microimage (Wolf & Scarbrough, 2012), we
obtained the total number of gallbladder epithelium cells to
be 1.61 0.23 10
8
. Besides the columnar epithelium,
gallbladder width is composed of a sub-epithelial stroma
and complex smooth fibromuscolar layers. Sub-epithelial
stroma and smooth fibromuscolar layers volumes were
calculated by morphological estimation (Bergman et al.,
2004). We calculated the interstitial Cajal-like cells
(4.94 0.04 10
5
) and other stromal gallbladder cells
(8.48 0.09 10
6
) starting from data reported by Hinescu
et al. (2007). We then calculated the total myocytes cell
number (considering the maximum length and the minimum
diameter of each cell (Portincasa et al., 2004)) by dividing the
smooth fibromuscolar layer volume (2.80 0.46 10
12
mm
3
)
by the single myocyte cell volume (1770 350 mm
3
), obtain-
ing 1.58 0.40 10
9
cells.
As for to the biliary ducts, we were able to estimate the
total epithelial cell number of the extra hepatic ducts
(7.03 5.30 10
7
) by dividing the total surface of the ducts
(Castelain et al., 1993; Khalil et al., 2005) by the cylindrical
epithelial cell basal surface.
Bones: Osteocytes total number
Since the total volume of bone tissue (BV) was not directly
measurable, it was necessary to compute it starting from total
skeleton weight (TW), extrapolated from the literature
(Trotter, 1954; Seale, 1959). The amount of cortical and
trabecular tissue was also investigated (77% and 23%,
respectively) (Malluche & Faugere, 1986). Based on
Figure 2. Human total cell number comparison. *Total cell number
calculated for the whole organ; **total cell number calculated only for
some cell types of the organ.
4 E. Bianconi et al. Ann Hum Biol, Early Online: 1–11
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micro-CT analysis, it was possible to obtain the average
porosity (bone volume over total volume fraction, BV/TV) of
both types of tissue and the correlation between bone porosity
and ash density (Tassani et al., 2011), defined as the ratio
between the bone weight and total geometrical volume of the
specimen, including empty spaces of porosity.
BV was computed as follows:
Ash Density ¼ m BV=TV þ b;
T
s
V ¼ TW Ash Density; and
B
s
V ¼ BV=TV T
s
V
where m is the slope of the linear regression (trabecular
1.04 g/cm
3
, cortical 1.15 g/cm
3
) and b is the intercept (0.03 g/
cm
3
for both trabecular and cortical bone), R
2
¼ 0.97 for
trabecular bone and R
2
¼ 0.91 for cortical bone (Tassani et al.,
2011). BV/TV is measured as the average value for the
trabecular (13 5%) and cortical (89 11%) bone. Knowing
the average ash density (trabecular 0.16 0.05 g/cm
3
, cor-
tical 1.06 0.14 g/cm
3
) of the two types of tissue and their
dry TW which is 3939 471 g (906 108 g trabecular
and 3033 363 g cortical) average from literature (Seale,
1959; Trotter, 1954), it is possible to compute total skel-
etal volume (T
s
V, trabecular 5618.04 1931.49 cm
3
, cor-
tical 2916.85 513.27 cm
3
) and total bone skeletal
volume (B
s
V, trabecular 722.56 377.99 cm
3
, cortical
2602.17 553.50 cm
3
).
The osteocyte (OCY) number estimated in a man less than
50 years old was expressed as a number for mm
2
of bone
surface (trabecular 98.97 1.24 cells/mm
2
cortical
56.34 1.69 cells/mm
2
) (Torres-Lagares et al., 2010). In
order to compute a volumetric analysis assuming bi-dimen-
sional cells distribution, a uniform distribution was hypothe-
sized. Therefore, linear density was first obtained (trabecular
9.95 0.09 cells/mm, cortical 7.51 0.16 cells/mm) and
finally the number of OCY for mm
3
was computed (trabecular
984.59 21.37 cells/mm
3
, cortical 422.89 21.97 cells/
mm
3
). Consequently the OCY total numbers for whole bone
tissue is 7.11 3.72 10
8
, trabecular and 1.10 0.24 10
9
,
cortical.
Bone marrow total cell number
The number of bone marrow nucleated cells was 1.11 10
10
(mean of 10 subjects, SD ¼ 5.25, count in rib sections) or
1.04 10
10
(mean of the same 10 subjects, SD ¼ 3.36, count
in crest aspirates) per body kilograms (Harrison, 1962). Using
the average of the two values, we have an estimate of
7.53 2.18 10
11
cells for the reference weight of 70 kg
(Irving, 2007).
Liver total cell number
Since hepatic volume is 1470 cm
3
(Irving, 2007), hepatocyte
volume is 4900 mm
3
(Prothero, 1982) and the parenchimal cell
percentage of the total liver is 80% (Borley, 2005b), we
estimated the total hepatocyte cell number at 2.41 10
11
.
Total stellate cells (2.41 10
10
) were calculated as 1/10 of
hepatocyte cells (Geerts, 2001), while total Kupffer cells
(9.63 10
10
) were obtained as 4-times the total stellate cells
(Dong et al., 2007). Therefore, the total cell number of the
liver is 3.61 10
11
.
Nervous system: Glial cells total number
Since the total glial cells in the nervous system are 10–50
times the neurons (Kandel et al., 2000; Standring et al., 2005)
(for details, see Table B1 in Appendix B), their number is
estimated as 3.00 0.66 10
12
.
Pancreas: Islet total cell number
The total number of islet cells (2.95 0.78 10
9
)was
calculated by multiplying the cell number per islet
1.56 0.02 10
3
(Pisania et al., 2010) and the mean
number of islets in the human pancreas equal to
1.89 0.5 10
6
(Meier et al., 2008).
Skin: Epidermal and dermal total cell number
We found the density of corneocytes, epidermal nucleate
cells, Langerhans cells and melanocytes in Hoath and Leahy
(2003). We obtained the relative total cell number by dividing
the standard human body surface (1.85 m
2
) (Irving, 2007) by
the specific density, to obtain an overall number of
1.76 0.44 10
11
cells. Epidermal Merkel cells resulted
3.62 10
9
as 0.20–5.00% compared to the total epidermal
cells (Boulais & Misery, 2007). By dividing the human body
surface by the specific densities of fibroblasts (Randolph &
Simon, 1998) and mast cells (Grimbaldeston et al., 2000) we
obtained an overall of 1.85 0.26 10
12
dermal cells.
Therefore, the total dermal and epidermal cell number were
found to be 2.03 0.30 10
12
(for details, see Appendix B,
Table B1).
Small intestine: Jejunum and ileum enterocytes total
number
To calculate the surface of the jejunum and the ileum of the
small intestine (0.35 m
2
), we considered them as two cylin-
ders. Their lengths and diameters are 2.00 m and 2.50 cm
(jejunum) and 3.00 m and 2.00 cm (ileum) (Borley, 2005c).
Then, considering the valvulae conniventes, the total surface
(1.04 m
2
) increases 3-fold (Teodori 1987). By an exact
graphyc reproduction (Cattaneo & Baratta, 1989), we
estimated 1000 3.40 cells per villus. Knowing that there
are 13 1 villi/mm
2
, the total number of cells covering them
is estimated at 1.35 10
10
. The total number of cells covering
the cryptae is 3.24 0.14 10
9
if we consider that they
represent 12/50 of the cryptae covering each villus (Weiss &
Greep, 1981; Cattaneo & Baratta, 1989) and that the
estimated number of cryptae and villi is roughly the same
(Cattaneo & Baratta, 1989). Therefore, the total enterocyte
cell number was calculated to be 1.67 0.71 10
10
.
Supradrenal gland total cell number
Normal mean adrenal gland volumes have been reported to be
5.70 (SD ¼ 4.90 and 1.90 for the right and left gland,
respectively) in a study that considered a group of 52 men
with an average age of 48.4 years (Geraghty et al., 2004).
Cortex and medulla zones represent 90% and 10%,
respectively, of the total gland volume. Reticularis, fasciculata
and glomerularis zones represent 7%, 78% and 15%, respect-
ively, of the cortex total volume (Martini 1994). Based on
these data, we calculated the volumes of the reticularis
DOI: 10.3109/03014460.2013.807878 Human cell number 5
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(0.36 cm
3
), fasciculata (4.00cm
3
), glomerularis (0.77 cm
3
)
and medulla (0.57cm
3
) zones. Cell volumes of the fasciculata,
glomerularis and medulla zones were 1200, 870 and 970 mm
3
,
respectively (Bocian-Sobkowska et al., 1997). These data
referred to new-born humans, but cell size does not change in
this organ during lifetime (Staton et al., 2004). We calculated
the radius (6.25 mm) of the reticularis zone cells, described as
round shaped (Borley, 2005d), by a morphological analysis of
a microimage (Hui et al., 2009) and then the volume
(1023 mm
3
). Finally, by dividing the single zone into the
specific cell type volumes, we obtained the mean of the
total cell number of the single zones, reported in Table B1.
The total cells of the two supradrenal glands are
1.03 0.16 10
10
(for details, see Appendix B, Table B1).
Vessels: Total endothelial cell number
The endothelium is composed of roughly 50–70 mm long and
10–30 mm wide cells, which cover the internal layer of the
vessel (Fe
´
le
´
tou, 2011). To calculate the total endothelial cell
number, we used two different approaches to estimate the
vessel’s internal surface and we then divided it for a single
cell area. For systemic capillaries, superior and inferior vena
cava, we considered their length as 8.00 10
9
cm (Loe &
Edwards, 2004), 7.00 cm (Testut & Latarjet, 1959; Johnson
et al., 2005), and 23.50 cm (Testut & Latarjet, 1959),
respectively, and their average diameter as 7.50 10
4
(Loe & Edwards, 2004), 3.00 cm (Ganong, 2006; Germann
& Stanfield, 2006), respectively. For the other vessels, we
estimated their length by using the blood volume occupying
the vessels, their diameter and assuming vessels were
cylindrical (Ganong, 2006; Germann & Stanfield, 2006;
Guyton & Hall, 2002; Mountcastle, 1980; Rhoodes &
Planzer, 2004; Testut & Latarjet, 1959). The calculations
led to a total number of 2.03 1.05 10
12
endothelial cells.
Current estimation of human total cell number
Our current estimation of human total cell number was
calculated only on a variety of organs and cell types, as listed
in Appendix B, Table B1. These partial data correspond to a
total number of 3.72 0.81 10
13
(Figure 2). This number
invalidates previous references, at least those indicating 10
12
as the human total cell number and creates the starting point
for a complete work that considers all the components of the
human body.
Discussion
The estimation of a reference cell count for the human whole
body was revealed to be not a trivial task. The results of our
bibliographical research show considerable variation in terms
of order of magnitude, which is not justifiable by inter-
individual differences (see Appendix A, Table A1).
Furthermore, we noted a consistent lack of citations of the
original literature providing the pertinent data in printed
books, online available books and websites. This is not totally
unexpected, following our difficulties in retrieving articles
discussing this specific issue by systematic searches in the
PubMed database. General estimations based on mean cell
volume or weight have not proved to be reliable, due to the
high variability in cell size, volume and weight among
different cell types and, in turn, due to high variability in
cellularity for each cell type in the human organism.
The most reliable way to determine the human number of
cells seems to be to sum the cell counts for individual organs.
This also presents the advantage of providing valuable
reference data for the study of each part of the human
organism. Data about static, kinetic and pathological cell
counts for organs and systems have been produced in the
context of a wide variety of fields in biology and medicine.
We have shown here that in many cases a precise count may
be obtained from the literature. However, several problems
have emerged while conducting this analysis. First, a major
difficulty was estimation of the number of stromal and
accessory cells in tissues and organs for which, instead, an
accurate count of parenchymal cells has been performed.
Secondly, it was difficult to obtain data for diffuse systems,
e.g. vessels or nerves, both in their different section and in
their global dimensions. In fact, a systematic survey of the
whole biomedical literature is not a trivial exercise, because
the pertinent data may have often have been disclosed in the
context of a particular study.
Finally, different sources of variability in cell number may
hamper estimation of a general reference number. Some organ
or tissue cellularity varies in function of sex, age or
evolutionary adaptation, not only because of a pathological
condition. For instance, erythrocyte cell count differs in males
and females as well as during pregnancy and in populations
adapted to high-altitudes. However, this appears to be a minor
problem because it is expected that these variations do not
reach an order of magnitude and a mean estimation remains a
reasonable end-point for this research. As reported in our
current partial estimation of total cell number of the ‘‘average
man’’ (Irving, 2007) we have an SD equal to 0.81 10
13
,
which is less than one order of magnitude.
We believe that knowledge of the cellularity of organs and
total body would be not only be culturally important but it
may also have biological and medical relevance, as demon-
strated by some key applications described below.
A quantitative model of development should explain how it
is possible to sustain a proliferation rate able to lead to a
whole human organism starting from a single cell. The wide
fields of cell growth and stem cell proliferation are potentially
included in this problem. Modelling of whole organs or
systems needs cell number data in order to produce afford-
able physiological views from the cells to the whole body.
For example, a recent report of ion transport by pulmon-
ary epithelia (Hollenhorst et al., 2011) cited quantitative
available data about the alveolar surface and cell number
(Crapo et al., 1982).
The determination of an organ or a tissue cell number is
relevant in medicine for diagnostic and prognostic proced-
ures. In fact, cellularity of biopsies leads to assessment of
specific pathologic states due to cell number deregulation.
For example, estimation of total number of hepatocytes in
cirrhotic patients gave a mean value of 1.72 10
11
(Imamura
et al., 1991) in comparison with the mean value of 2.40 10
11
reported by us for a healthy organ. In the case of blood cell
counts, accessibility of tissue and standardization of method-
ology has led to quantitative and qualitative characterization
6 E. Bianconi et al. Ann Hum Biol, Early Online: 1–11
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of cell types and sub-types. In the same way, it would be
important to know the cell number of other tissues and organs,
along with the mechanisms regulating it, which could be
crucial in understanding the biology and kinetics of cancer
(Albanes & Winick, 1988), as well as the development of
many other human diseases. For instance, dysregulation of
organ size control has been implicated in diabetes and
hypertrophy (Yang & Xu, 2011) and trisomy 21, where the
relatively greater volume of the cell population of heart,
skeletal muscle, liver and brain is only a partial compensation
for the smaller cell number and not strong enough to produce
normal organ mass (Landing & Shankle, 1995). Moreover,
estimation of cellularity, organ and cell size of diseased
organs would benefit modern strategies of human biological
and disease research. In fact, the size of some organs can
decrease as a result of malnutrition and disease during
gestation or critical growth periods. For example, it has been
proposed that the number of adult nephrons may be
determined during renal development in utero and may be
related to foetal malnutrition (Barker, 1995; Lackland, 2005).
Finally, from an evolutionary point of view, data about cell
number in different species could allow a measure of
organism and organ complexity valuable in order to classify
and understand inter-species variability at phenotypic level
(Herculano-Houzel, 2011; Kothari et al., 1978). The formal
description of cell types and number of different organisms
could be valuable, in conjunction with other measures of
complexity such as gene number and function (Szathmary
et al., 2001), in order to develop better indices quantitatively
related to the ‘‘complexity’’ of an organism (Grizzi &
Chiriva-Internati, 2005).
Since we believe that the total human cell number may be
obtained by summing all data related to the single organs and
that the systematic work on each human section is complex
and requires a meticulous work, we believe that this issue is
an ideal candidate for a collaborative effort.
The problems outlined here could stimulate attainment and
publication of useful data worldwide, in order to provide a
systematic organ-by-organ view of human organism cellular-
ity and a final detailed estimation of the total cell number in a
standard human adult. Ideally, the last step could be
preparation of a forum paper and an on-line database resource
summarizing the complete picture by integrating data from
different expert contributors. With this aim, we release our
current estimations (Figure 2) so that they are available for
correction, integration and completion from any interested
researcher. These final results could be, in future develop-
ments, integrated into or related to formal description of
anatomical entities provided by ongoing attempts to formalize
anatomical data through the creation of ontologies (Baldock
& Burger, 2005; Hayamizu et al., 2005).
Conclusions
We have shown the importance and the usefulness of
searching for a reference number of the cells present in a
human body, providing hypotheses for a solution of the
problem. Our current estimation of 3.72 10
13
cells for a
variety of organs and cell types is higher than some
estimations found in the literature. We believe that our initial
reference table for cell number in the human body, when
completed, possibly with a common effort, will have many
useful applications in all biomedical fields needing quantita-
tive measurement in order to build structural, functional,
pathological and comparative models of human organs and of
the whole body.
Acknowledgements
The authors wish to thank Paolo Comeglio and Lucia Mancini for
helping with the revision of the manuscript.
Declaration of interest
The authors report no conflicts of interest. The authors alone are
responsible for the content and writing of the paper.
This work was partially supported by a Marie Curie Intra
European Fellowship within the 7th European Community
Framework Programme (project number: PIEF-GA-2009-253924;
acronym: MOSAIC).
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Appendix A
In order to find primary literature articles with information about the total cell number of a human organism, we systematically searched the PubMed
database and the available printed and on line NCBI and Google books. Only data supported by a primary source are presented here.
Appendix B
We present here the results on the cell number of specific systems, organs or cell types obtained to date with our research. Some of the values were
obtained directly from an in-depth bibliographical search, other data needed an integration of some or all methods described in the manuscript. In the
‘‘SD’’ column we indicate the standard deviation of the cell type calculations as obtained from available bibliographical data; we use ‘‘NA’’ to indicate
that no data were available to calculate an error estimate. In the ‘‘References’’ column we indicate the bibliographical sources used for our estimations.
Table A1. Estimations of human total cell number from bibliographical search.
Cell number Reference Source
10
12
Hanslmeier (2009) Online book
10
13
Conlon & Raff (1999) Original article (Baserga, 1985)*
Boncinelli (2007) Printed book
Asimov (1963) Printed book
New Encyclopaedia Britannica (1976) Printed book
Van Amerongen et al. (1979) Printed book
Freitas (1999) Printed book
Baserga (1985) Printed book
Alberts et al. (2002) Online book
Cooper (2000) Online book
Griffiths et al. (2000) Online book
Baron (1996) Online book
Brown (2002) Online book
Griffiths et al. (1999) Online book
Goodsell (2010) Online book
Ratner & Bankman (2009) Online book
E-Notes Study Matter (2011) Website (Asimov, 1963; New Encyclopaedia Britannica, 1976;
Van Amerongen et al., 1979)y
Bry et al. (1995) Website (Freitas, 1999)y
10
14
Hood and Galas (2003) Original article
Strachan and Read (1999) Printed book
National Institutes of Health (2007) Online book
Lodish et al. (2000) Online book
Pittman (2011) Online book
Claybourne (2006) Online book
Samaras et al. (2007) Online book
The Carnegie Library of Pittsburgh (2011) Online book
Swenson (2000) Online book
Ehrenfeucht et al. (2004) Online book
10
16
Zweiger (2002) Printed book
Frank (2007) Online book
*References are cited by the specific ‘‘Original article’’.
yReferences are cited by the specific ‘‘Website’’.
Table B1. Total cell number of organs or cell types.
Organ/system Cell type
Mean total
cell number SD References
Adipose tissue Adipocytes 5.00 10
10
2.30 10
10
Spalding et al. (2008)*
Articular cartilages Femoral cartilage cells 1.49 10
8
0.46 10
8
Baysal et al. (2004); Stockwell (1971)y
Humeral head cartilage cells 1.23 10
8
0.35 10
8
Stockwell (1971); Vanwanseele et al. (2004)y
Talus cartilage cells 8.06 10
7
1.56 10
7
Stockwell (1971); Millington et al. (2007)y
Biliary system Biliary ducts epithelial cells 7.03 10
7
5.30 10
7
Bergman et al. (2004); Borley (2005a); Castelain
er al. (1993); Khalil et al. (2005); Wolf &
Scarbrough (2012)y
Gallbladder epithelial cells 1.61 10
8
0.23 10
8
Bergman et al. (2004); Borley (2005a); Irving
(2007); Wolf & Scarbrough (2012)y
Gallbladder Interstitial
Cajal-like cells
4.94 10
5
0.05 10
5
Hinescu et al. (2007); Irving (2007)y
Gallbladder smooth myocytes 1.58 10
9
0.40 10
9
Irving (2007); Portincasa et al. (2004)y
(continued )
10 E. Bianconi et al. Ann Hum Biol, Early Online: 1–11
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Table B1. Continued
Organ/system Cell type
Mean total
cell number SD References
Gallbladder other stromal cells 8.48 10
6
0.09 10
6
Hinescu et al. (2007)y
Blood Erythrocytes 2.63 10
13
0.51 10
13
Alberts et al. (2002); Loe & Edwards (2004);
Young & Heath (2001)*
Leucocytes 5.17 10
10
2.43 10
10
Alberts et al. (2002); Young & Heath (2001);
Stock & Hoffman (2000)*
Platelets 1.45 10
12
0.57 10
12
Alberts et al. (2002); Young & Heath (2001)*
Bone Cortical osteocytes 1.10 10
9
0.24 10
9
Malluche & Faugere (1986); Seale (1959);
Tassani et al. (2011); Trotter (1954); Torres-
Lagares et al. (2010)y
Trabecular osteocytes 7.11 10
8
3.72 10
8
Malluche & Faugere (1986); Seale (1959);
Tassani et al. (2011); Trotter (1954); Torres-
Lagares et al. (2010)y
Bone marrow Nucleate cells 7.53 10
11
2.18 10
11
Harrison (1962)y
Heart Connective tissue cells 4.00 10
9
NA Adler & Costabel (1975)*
Heart muscle cells 2.00 10
9
NA Adler & Costabel (1975)*
Kidney Glomerulus total cells 1.03 10
10
0.36 10
10
Steffes et al. (2001)*
Liver Hepatocytes 2.41 10
11
NA Borley (2005b); Irving (2007); Prothero (1982)y
Kupffer cells 9.63 10
10
NA Dong et al. (2007)y
Stellate cells 2.41 10
10
NA Geerts (2001)y
Lungs, bronchi,
bronchioles
Alveolar cells (type I) 3.86 10
10
0.95 10
10
Crapo et al. (1982); Stone et al. (1992)*
Alveolar cells (type II) 6.99 10
10
1.45 10
10
Crapo et al. (1982); Stone et al. (1992)*
Alveolar macrophages 2.90 10
10
0.73 10
10
Crapo et al. (1982); Stone et al. (1992)*
Basal cells 4.32 10
9
0.95 10
9
Mercer at al. (1994)*
Ciliated cells 7.68 10
9
1.62 10
9
Mercer at al. (1994)*
Endothelial cells 1.41 10
11
0.30 10
11
Crapo et al. (1982); Stone et al. (1992)*
Goblet cells 1.74 10
9
0.51 10
9
Mercer at al. (1994)*
Indeterminate bronchial/
bronchiolar cells
3.30 10
9
1.00 10
9
Mercer at al. (1994)*
Interstitial cells 1.37 10
11
0.16 10
11
Crapo et al. (1982); Stone et al. (1992)*
Other bronchial/bronchiolar
secretory cells
4.49 10
8
1.97 10
8
Mercer at al. (1994)*
Preciliated cells 1.03 10
9
0.34 10
9
Mercer at al. (1994)*
Nervous system Glial cells 3.00 10
12
0.66 10
12
Kandel et al. (2000); Standring et al. (2005)y
Neurons 1.00 10
11
NA Purves et al. (2001); Williams & Herrup (1988)*
Pancreas Islet cells 2.95 10
9
0.78 10
9
Meier et al. (2008); Pisania et al. (2010)y
Skeletal muscle Muscle fibers 2.50 10
8
NA Howell & Fulton (1949)*
Satellite cells 1.50 10
10
0.17 10
10
Morgan & Partridge (2003)*
Skin Dermal fibroblasts 1.85 10
12
0.26 10
12
Irving (2007); Randolph & Simon (1998)y
Dermal mast cells 4.81 10
7
2.82 10
7
Grimbaldeston et al. (2000); Irving (2007)y
Epidermal corneocytes 3.29 10
10
0.47 10
10
Hoath & Leahy (2003); Irving (2007)y
Epidermal nucleate cells 1.37 10
11
0.39 10
11
Hoath & Leahy (2003); Irving (2007)y
Epidermal Langerhans cells 2.58 10
9
0.65 10
9
Hoath and Leahy (2003); Irving (2007)y
Epidermal melanocytes 3.80 10
9
NA Hoath & Leahy (2003); Irving (2007)y
Epidermal Merkel cells 3.62 10
9
NA Boulais & Misery (2007)y
Small intestine Enterocytes 1.67 10
10
0.71 10
10
Borley (2005c); Cattaneo & Baratta (1989);
Teodori (1987); Weiss & Greep (1981)y
Stomach G-cells 1.04 10
7
0.30 10
7
Royston et al. (1978)*
Parietal cells 1.09 10
9
0.08 10
9
Cox (1952); Naik et al. (1971)*
Supradrenal gland Medullary cells 1.18 10
9
0.18 10
9
Bocian-Sobkowska et al. (1997); Geraghty et al.
(2004); Martini (1994)y
Zona fasciculata cells 6.67 10
9
1.02 10
9
Bocian-Sobkowska et al. (1997); Geraghty et al.
(2004); Martini (1994)y
Zona glomerularis cells 1.77 10
9
0.27 10
9
Bocian-Sobkowska et al. (1997); Geraghty et al.
(2004); Martini (1994)y
Zona reticularis cells 7.02 10
9
0.11 10
9
Bocian-Sobkowska et al. (1997); Geraghty et al.
(2004); Hui et al. (2009); Martini (1994)y
Thyroid Clear cells 8.70 10
5
NA Gibson et al. (1982)*
Follicular cells 1.00 10
10
NA Gibson et al. (1982)*
Vessels Endothelial cells 2.54 10
12
1.05 10
12
Fe
´
le
´
tou (2011); Ganong (2006); Germann &
Stanfield (2006); Guyton & Hall (2002);
Johnson et al. (2005); Loe & Edwards (2004);
Mountcastle (1980); Rhoodes & Planzer
(2004); Testut & Latarjet (1959)y
Bibliographical method is highlighted with *, while an integration of methods with y.
DOI: 10.3109/03014460.2013.807878 Human cell number 11
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