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JOURNAL OF WOUND CARE VOL 18, NO 11, NOVEMBER 2009462
The healing properties of placental extract are well established in various skin
conditions, including chronic wounds, pressure ulcers and burns. However, its
biochemical composition and mechanisms of action are still largely unknown
human placental extract; therapeutic efficacy; wound healing
T
he placenta is as a natural storehouse of
biologically active compounds including
hormones, proteins, peptides, growth fac-
tors, nucleic acids, glycosaminoglycans
(GAGs) and polydeoxyribonucleotides
(PDRNs) that are crucial for fetal growth and devel-
opment.1 It protects the fetus against fatal infections,
mutagens, carcinogens and teratogens, and creates a
cushioning effect against mechanical thrust. It is not
surprising, therefore, that plancental extracts also
have healing properties.
Placental extract has been used over the ages to
treat various ailments, including ulcers.1,2 Age-old
practices include its topical use on burn injuries,
chronic wounds, pressure ulcers and as a post-surgi-
cal dressing.3 The composition of the extract
depends on the method of preparation. Aqueous
and hydroalcoholic extracts are mainly used in clin-
ical practice, but only aqueous extract has healing
properties.4 This paper discusses the biochemical
components of the human aqueous placenta extract
and their clinical efficacy. The primary focus is on
the extract’s wound-healing properties and probable
mechanism of action.
Placental preparations
Placental preparations can be broadly classified into
two types: aqueous and hydroalcoholic. The com-
ponents depend on the method of preparation.
Aqueous extract contains polar molecules such as
peptides/proteins, small organic components such
as amino acids, nucleotides, (PDRNs), carbohydrates
and trace amounts of lipids, as these are mostly
bound to proteins that are comparatively soluble in
an aqueous medium.5
Conversely, less polar and hydrophobic lipids are
likely to be present in hydroalcoholic extract.
Indeed, chemical analysis has revealed the presence
of glycosphingolipids, cholesterol, triglycerides,
high-density lipoproteins, carbohydrates, sialic
acids, amino acids, nucleotides, carotenes, vitamins
and trace amounts of low-molecular-weight pro-
teins/peptides, as well as hydrophobic amino acids,
which are soluble in a less polar solvent.6
Placental extract as a wound healer
Cell adhesion
This section refers to the aqueous extract of human
placenta. Spectroscopic studies and thin-layer chro-
matography have also shown that placental extract
contains the coenzyme NADPH,7 which improves
the surface structure of ageing skin and inhibits
photocarcinogenesis.8,9 Beneficial effects on epider-
mal function have also been documented.10
The peptide 7.2 kDa has been purified from aque-
ous placental extract. A partial amino acid sequence,
derived from mass spectrometric analysis, revealed
its homology with human fibronectin type-III,
which is a component of the extracellular matrix
(ECM). It is possible, therefore, that the peptide 7.2
kDa also promotes healing.11
It has been documented that fibronectin peptide
can mimic an intact protein as a substrate for cell
migration. If the peptide is adsorbed to a surface or
attached covalently to a carrier molecule, it can be
bound by a cell-surface integrin, which can mediate
direct cell adhesion or cell migration.12 Indeed,
binding of fibronectin peptides can augment
integrin signalling and induce the expression of col-
lagenase or activate cell-to-cell adhesion in some
cell types, facilitating wound healing.13 It has also
been reported that oncofetal fibronectin is involved
in endothelial cell proliferation, promoting wound
healing more efficiently than normal fibronectin.14
The fibronectin type-III-like peptide showed sig-
nificant cell-adhesion properties on mouse perito-
neal macrophages and P388D1 cultured macrophage
cell line.15
Nitric oxide (NO) has multiple effects that pro-
mote wound healing at the molecular, cellular and
physiological level.16,17 NO-mediated cellular signal-
ing may enhance wound repair by increasing the
supply of oxygen to tissue through angiogenesis.18
NO is produced from L-arginine and NADPH in the
P.D. Chakraborty1,2
D. De1
S. Bandyopadhyay2
D. Bhattacharyya 1
1 Division of Structural
Biology and
Bioinformatics, Indian
Institute of Chemical
Biology, Jadavpur,
Calcutta, India;
2 M/s Albert David,
Calcutta, India.
Email: p_datt@rediffmail.
com
Human aqueous placental extract
as a wound healer
practice
JOURNAL OF WOUND CARE VOL 18, NO 11, NOVEMBER 2009464
presence of oxide synthase enzymes. Indeed, the
metabolism of NADPH is critical to the synthesis of
nitric oxide.19
The induction of NO by mouse peritoneal macro-
phages in aqueous placental extract has been inves-
tigated. The results showed that increased NO pro-
duction was concomitant with a decrease in NADPH
in the applied placental extract. This indicates that
the NADPH pool of placental extract is metabolised,
further demonstrating its biological potency.20
Antibacterial action
Placental extract has also been shown to induce
interferon-g (IFN-g) production by macrophages.16,21
IFN-g plays a major role in innate or adaptive immu-
nity and in inflammation.21 Human and animal
models have shown that placental extract has an
immunotropic or immunostimulating action both
at the cellular and humoral levels. The extract prob-
ably increases IgG and IgM antibodies at the humor-
al level and total lymphokines at the cellular level.22
IgG and IgM activate the classical pathway of the
complement system. They produce specific anti-
biodies, thereby neutralising viruses and lysing
Gram-negative bacteria. As wounds are susceptible
to bacterial growth, this action is critical for efficient
healing.
Regulation of protease activity
Proteases regulate the balance between tissue degra-
dation and regeneration. Delayed removal of necrot-
ic tissue due to insufficient protease levels impairs
healing. However, excess proteolytic activity during
proliferation interferes with the accumulation of
substrates for healing. A number of matrix metallo-
proteases and their inhibitors control these intricate
processes.23 Regulation of proteolytic activity is
therefore critical for efficient wound repair.
It has been observed that aqueous placental
extract regulates proteolytic activity of certain pro-
teases involved in healing.24 Furthermore, it stabi-
lises some proteolytic enzymes against their auto-
digestion, enhancing their efficiency and thereby
facilitating wound healing.24
Proportionate mixing of the extract with proteo-
lytic enzymes and then evaluating its effect on
wound healing may be a promising avenue for
future research.
Anti-inflammatory properties
Clinical evaluation of the extract has revealed that it
has anti-platelet aggregation activity.25 Platelet
aggregation is an important pathogenic marker of
inflammaton. Human placental extract also exhibits
an anti-inflammatory response, probably by either
inhibiting/inactiving chemical mediators or directly
modulating prostaglandin (PG) production. PG may
induce or inhibit platelet aggregation and constrict
dilated blood vessels. Placental extract may there-
fore modulate PG production by inhibiting platelet
aggregation to exert its anti-inflammatory effects.25
Kinins, which are chemical mediators of non-
immunological inflammation, have two membrane
receptors, B1 and B2. In a cotton-pellet-induced
subacute inflammation model, the extract inhibited
the B1-receptor, reducing its anti-inflammatory
effect. It also helps activate the clotting cascade fol-
lowing trauma, which results in platelet activation
followed by aggregation.
Serotonin (5-HT), which is present in mast cells, is
possibly more potent than histamine in increasing
vascular permeability in rats.26 As considerable
reduction of inflammation was observed in 5-HT
pretreated rats following application of the extract,
it might be suggested that the inhibitory action was
5-HT mediated. The clinical study of platelet aggre-
gation indicates that placental extract can either
inhibit PG synthesis pathway or 5-HT release.25
Collagen synthesis
Role of placental extract in collagen synthesis dur-
ing wound wound healing was studied by wound-
ing Charles Foster albino rats. Its effects on wound
size, healing times and tensile strength were observed
by measuring the rate of wound contraction and
performing histopathological studies.27 The extract
was shown to stimulate collagen synthesis in vivo.
The significant increase in tensile strength and tis-
sue DNA in the animals given the extract (intramus-
cularly) indicates it was associated with marked col-
lagen synthesis. The efficiency of collagen formation
depends mainly on the synthesis of hydroxyproline,
which was also high in rats given the extract.28 This
is supported by histopathological analysis, which
showed maximum accumulation of collagen fibrils
and epithelialisation.27
Clinical efficacy
It appears that peptides within placental extract are
primarily involved in wound healing, whereas DNA
fragments and bio-organic molecules such as
NADPH play a role in defence mechanisms such as
the prevention of secondary infections. Other com-
ponents of the extract have yet to be identified.
The injectable form of placental extract has been
reported to be an effective and inexpensive stimula-
tor of granulation tissue, and superior to the use of
povidone-iodine.29
A dressing containing human placental extract
was found to be effective on chronic varicose
ulcers.2,30 The effect of a gel form of the extract, used
in combination with dermabrasion, has also been
studied.31 For burn cases, many physicians prefer
direct application of the extract over the wounded
area to reduce burning sensation and pain, protect
against infection and initiate healing.25,30 The
practice
s
JOURNAL OF WOUND CARE VOL 18, NO 11, NOVEMBER 2009 465
wound-healing potency of the extract is thus clini-
cally well established,2,25,27,30 but the active compo-
nents present and molecular mechanisms involved
in the healing process still need to be defined.
Source of growth factors
Human placenta is a rich source of growth factors
and plays a role in their upregulation or increased
synthesis. Fibroblast growth factor (FGFs) and stim-
ulators of endothelial cell growth are present in the
extract.32 FGF is a key factor in angiogenesis, dermal
repair and epithelialisation.33 It has been reported
that the extract augments protein levels of both FGF
and transforming growth factor (TGF).32 TGF-beta
stimulates the migration of keratinocytes and fibrob-
lasts,34 and enhances the production of ECM com-
ponents such as collagen,35 fibronectin36 and gly-
cosaminoglycan.37
The placenta growth factor (PlGF) is a member of
the vascular endothelial growth factor (VEGF) fami-
ly, which is involved in the promotion of angiogen-
esis. PlGF, which is thought to be present in the
extract, accelerates wound closure, with histologi-
cally well-reconstructed skin architecture, and
enhances angiogenesis. PlGF of low immunogenicity
accelerates both normal and delayed skin wound.38
Bacteriostatic activities
Aqueous placental extract has both bacteriostatic
and fungicidal activities.39 In in vitro tests, the extract
inhibited the growth of pathogens including
Escherichia coli and Staphylococcus aureus, and fungi
including Saccharomyces cerevisiae, Kluyveromyces fra-
gilis and Candida albicans.40 Although the mecha-
nism of such microbial growth inhibition has not
been studied, it is hypothesised that the PDRNs
present in the extract enter the microbes and inter-
fere with their ability to replicate.40 Aqueous placen-
tal extract also prevented the growth of clinically
isolated bacteria, such as E. coli, from urine and
blood culture and S. aureus from pus.26
Drug-resistant strains, such as E. coli DH5a and
Pseudomonas aeruginosa CamR, have also been sig-
nificantly inhibited by the extract.40 A dose-depend-
ent response was observed.
Benets of aqueous placental extract
Aqueous extract is the only type of placental extract
that promotes wound healing.32 This could be
because it is a rich source of various peptides, amino
acids, nucleotides, PDRNs and carbohydrates, which
are believed to support the healing process.1 The
potency of the placental extract lies in the fact that
it not only reduces the inflammatory phase of heal-
ing, and lessens the microbial burden,40 but also
assists cell migration,41 ECM formation and tissue
regeneration, thereby ensuring sequential steps of
healing.11,16,22 It is also reported that the extract pro-
motes fibrogenesis (development or proliferation of
fibres or fibrous tissue), neoangiogenesis and epithe-
lialisation.22
Use of placental products
A wide variety of placental products manufactured
in different countries are available (Table 1). A good
number are used for therapeutic purposes and the
rest mainly as skin creams and lotions. The thera-
peutic products are mostly injectable, although a
few can be taken orally. These products are market-
ed as licensed drugs, comply with the Good Manu-
facturing Process (GMP) certificate and have approv-
als from various regulatory authorities.
Placentrex (M/s Albert David, India) has been on
the market for more than 60 years. Several recent
biochemical evidences support the functionality of
the drug.1,2,20,32,40,42,43 Other drugs such as Laennac44
(Japan Bioproducts Industry, Japan) and Melsmon
(Melsmon Pharmaceuticals, Japan) have also been
clinically tested and scientifically documented,45
but they show different therapeutic activities. The
cosmetic products generally have a complex com-
position. There are fewer scientific evaluations on
these products as this is not a legal requirement.
Of the substances used in cosmetic products, the
freeze-dried placental extract seems to be the most
successful in strengthening flaccid connective tis-
sue.46 Placental extract improves the skin’s blood
circulation and metabolism, and increases the fre-
quency of cell division in the skin.47 It is a rich source
of bioactive peptides and amino acids.48
Human placental extract is widely used in Japan,
Korea, Germany, Switzerland and New Zealand for
tissue regeneration and wound healing. The Centro
de Histoterapia Placentaria in Havana, Cuba, makes
placental products for various skin complaints. The
Amsterdam-based Placenta Research Foundation
has discovered, while researching the preservation
of autologous placenta, some interesting findings
and translated them into a life-extension product.
Placenta Bank in the Netherlands will store the
afterbirth, and subsequent placental extract, for the
mother’s or child’s future use.48
Conclusion
Further study is needed to characterise the active
components present in different placental prepara-
tions and correlate them with their therapeutic
action. The extraction procedures need to be stand-
ardised so that the therapeutically active compo-
nents are consistently incorporated into the extract.
The bioactive peptides and growth factors present
in the extract need to be identified, characterised
and their mode of action determined. The lipid and
nucleotide components also need to be identified
and profiled. Other biologically important compo-
nents identified include fibronectin type-III-like
References
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JOURNAL OF WOUND CARE VOL 18, NO 11, NOVEMBER 2009466
Table 1. Different Placental products used as medicine and cosmetics
Product name Manufacturer Country Clinical application Administration
Placentrex M/s Albert David India Wound healing Intramuscular injection,
topical gel and lotion
Laennac Japan Bioproducts Japan Hepatoprotection, Intramuscular injection
Industry skin rejuvenation and
whitening
Melsmon Cell Melsmon Pharmaceuticals Japan Cell revitalisation and Intramuscular injection
Revitalization Extract promoting neoangeogenesis
MF II - Switzerland Cellular regeneration Intramuscular injection
and tissue healing and capsules for oral
intake
Placenta ampoule DIO International Korea Skin renewal Intramuscular injection
Sheep Placenta Deep Blue Health New Zealand Dietary food supplement Capsules for oral intake
Sheep Placenta Careline Group Pty. Australia Anti-aging, skin Capsules for oral intake,
revitalization, allergy skin cream for
resistance topical use
Sheep Placenta Soft Guangzhou Boan Health China Nutritional supplement Capsules for oral intake
Gel Products
Sheep Placenta Anzchem Pty. Australia Promote cell growth, Water soluble powder
Extract Powder hormone regulation and suitable for manufacture
skin hydration of capsules, lotions and
creams
Lamb Placenta Soft Guangdong Luck-sun China Skin rejuvenation and Capsules for oral intake
Capsules Medicine nutritional supplement
Placenta Hydrolysate Hangzhou Huajin Pharma China Stimulates proliferation of —
hepatocytes
Sheep Placenta Youzhiyou Biotechnology China Skin regenration and For topical use
Extract whitening factor
Larins Placenta Untouched Native New Zealand Rejuvenation of the skin, Skin cream for topical
Cream and protection from use
environmental damage
and scar reduction
Regenerating Active Nelson Laboratory New Zealand Rejuvenation of the skin Topical skin cream and
eye serum
Placenta BB cream Dermal Korea Korea Blemish balm for sensitive Skin cream for topical
skin use
Gold Rejuvenating Ecowool New Zealand Anti-ageing Skin serum for topical
Placental Serum use
Placenta range Lanocreme New Zealand Cell renewal, improve skin Skin cream and lotion
elasticity and skin for topical use
nourishment
EMK Placental Skin EMK Products, LLC US Anti-ageing, and skin and Skin cream, lotion,
Care Products hair rejuvenation serum and injections
practice
JOURNAL OF WOUND CARE VOL 18, NO 11, NOVEMBER 2009 467
peptide, PDRN and NADPH. It is also possible that
other, as yet unidentified peptides or small mole-
cules present in various preparations of the extract,
may play promote wound healing.
An advantage of placental extraction is the con-
sistency of the placenta composition. The extract
contains multipotent molecules, which show thera-
peutic efficacy at very low concentrations. To
achieve an understanding of the complex array of
molecules involved, it is necessary to concentrate
the extract. However, concentrating the extract for
characterising individual molecules to the limit of
detection increases molecular association and aggre-
gation. This problem can be overcome by using
various modes of high-resolution techniques. Once
the active components are identified and their
mechanisms of action are defined, newer formula-
tions of the extract could be prepared with height-
ened potency. n
A research program
operating at the Indian
Institute of Chemical
Biology (CSIR) and
sponsored by M/s Albert
David Ltd. is
acknowledged by the
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