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MILITARY MEDICINE, 185, S1:404, 2020
Whole-Body Vibration Training Increases Stem/Progenitor Cell
Circulation Levels and May Attenuate Inammation
Yameena Jawed, MD*; Eleni Beli, PhD†; Keith March, PhD, MD‡;
Anthony Kaleth, PhD§; M. Terry Loghmani, PhD, PT
ABSTRACT Introduction: Whole-body vibration training (WBVT) may benefit individuals with difficulty partici-
pating in physical exercise. The objective was to explore the effects of WBVT on circulating stem/progenitor cell
(CPC) and cytokine levels. Methods: Healthy male subjects each performed three activities randomly on separate
days: (1) standing platform vibration, (2) repetitive leg squat exercise; and (3) in combination. Pre- and post-activity
blood samples were drawn. Cell populations were characterized using flow cytometry. Biomarkers were analyzed using
enzyme-linked immunosorbent assays. Results: CPC levels increased significantly 21% with exercise alone (1465 ±202–
1770 ±221 cells/mL; P=0.017) and 33% with vibration alone in younger participants (1918 ±341–2559 ±496;
P=0.02). Angiogenic CPCs increased 39% during combined activity in younger (633 ±128–882 ±181; P=0.05).
Non-angiogenic CPCs increased 42% with vibration alone in younger (1181 ±222–1677 ±342; P=0.04), but 32%
with exercise alone in older participants (801 ±251–1053 ±325; P=0.05). With vibration alone, anti-inflammatory
cytokine interleukin-10 increased significantly (P<0.03), although inflammatory interleukin-6 decreased (P=0.056);
tumor necrosis factor-alpha (P<0.01) and vascular endothelial growth factor levels increased (P<0.005), which are
synergistically pro-angiogenic. Conclusions: WBVT may have positive vascular and anti-inflammatory effects. WBVT
could augment or serve as an exercise surrogate in warfighters and others who cannot fully participate in exercise
programs, having important implications in military health.
INTRODUCTION
Cardiovascular disease (CVD) results from the development
of atherosclerosis and is the leading cause of death in the
United States, killing on average one U.S. adult every 39 sec-
onds.1,2The beneficial effects of regular exercise are well
documented, including reductions in blood pressure (BP),
decreased inflammation, and reduced cardiovascular-related
morbidity and mortality.3,4However, the underlying mecha-
nisms for the beneficial effects of exercise are still not fully
understood. Furthermore, participation in exercise protocols
by individuals who are traumatized or debilitated can be
*Division of Pulmonary, Critical Care, Sleep and Occupational Medicine,
School of Medicine, Indiana University, 541 Clinical Dr., CL 260, Indianapo-
lis, IN 46202
†Indiana Diabetes Research Center, School of Medicine, Indiana Univer-
sity, 635 Barnhill Dr., MS 2031A, Indianapolis, IN 46202
‡Center for Regenerative Medicine, College of Medicine, University of
Florida, M-108 Health Science Center, P.O. Box 100216, Gainesville, FL
32610
§Department of Kinesiology, School of Health and Human Sciences,
Indiana University, 901 W. New York Street, Indianapolis, IN 46202
Department of Physical Therapy, School of Health and Human Sciences,
Indiana University, 1140 W. Michigan Street, CF320A, Indianapolis, IN
46202
Presented as an oral talk at the 2018 Military Health System Research
Symposium, August 2018, Kissimmee, FL; abstract # MHSRS-18-2003.
The views expressed in this article are those of the authors and do not
necessarily represent the official position of policy of the U.S. Government,
the department of defense, or the Department of the Air Force.
doi:10.1093/milmed/usz247
© Association of Military Surgeons of the United States 2020. All rights
reserved. For permissions, please e-mail: journals.permissions@oup.com.
difficult or impossible, such as is the case with some warfight-
ers and veterans.
Recent research suggests that acute bouts of exercise are
associated with increased levels of particular circulating
cells (endothelial progenitor/stem cells, EPCs) known to
have a significant role in the maintenance of vascular wall
integrity and overall cardiovascular health.5,6Several studies
have confirmed a strong relationship between exercise and
circulating EPCs, giving rise to the hypothesis that the
beneficial outcomes of regular exercise are because of
the deployment of EPCs to serve in repair of damaged
(or diseased) vessel walls. In middle-aged volunteers with
chronic diseases, exercise stress testing increased AC133+/VE
Cadherin+EPC counts fourfold (from 66 to 236 cells/mL
blood) and the number of isolated AC133+/VE Cadherin−
circulating angiogenic cells increased 2.5-fold.6In patients
with coronary artery disease, exercising for 28 days showed
an up-regulation of CD34+/KDR+EPCs in peripheral blood
of 78% ±34% and a decrease in apoptosis. Moderate short-
term running for 10 minutes did not upregulate EPC counts.7
Circulating progenitor cells (CPCs) (CD34+CD45dim)and
EPCs (CD34+/KDR+/CD45dim) were higher 2 hour post-
resistance exercise.8
Vibration training, also known as biomechanical stimu-
lation, and biomechanical oscillation, is a training method
that employs low amplitude and low frequency mechanical
stimulation. A single bout of low intensity vibration increases
systemic and regional (ie, skin) blood flow. The rapid con-
traction and relaxation of the muscles at 20 to 50 times per
second works as a pump on the blood vessels and lymphatic
vessels increasing the speed of the blood flow throughout
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Vibration Increases Circulating Stem Cell Levels
FIGURE 1. Activity performance. Each subject was randomly assigned to perform one of three activities on separate days (spaced 4–7 days apart): (A)
standing on a vx, (B) sq, and (C) in combination (vx and sq). Subjects wore an additional 15% body weight vest when squatting.
the body. Whole-body vibration training (WBVT) has been
shown to be beneficial for the musculoskeletal system (eg,
muscular strength, power, and bone mineral density), and pos-
tural control, decreased fall risk, and balance in old people.9–11
It promotes osteogenic differentiation of rat bone marrow
mesenchymal stem cells (MSC) in vitro.12 In a murine model,
brief exposure to mechanical signals diminished the conse-
quences of diabetes and obesity, restoring bone structure and
normalizing B-cell populations.13 Vibration training also had
beneficial effects on wound healing by enhancing angiogene-
sis and granulation tissue formation, and these changes were
associated with increases in pro-angiogenic growth factors in
diabetic mice.14 Vascular endothelial growth factor (VEGF)
showed a significant increase immediately following the com-
bination of cycling exercise and exposure to exogenously
induced vibrations, but not after cycling exercise alone.15
Acute bouts of vibration exercise have shown to improve oxy-
gen uptake,16 increased blood volume,17 and reduce arterial
stiffness.18
Despite the known benefits of exercise, adherence to
exercise programs is often problematic, particularly for older
adults, individuals with difficulty performing ambulatory
activities or cycling (eg, individuals diagnosed with peripheral
vascular disease, cognitive impairment, or arthritis), trauma
victims, or individuals in intensive/critical care units.19,20 In
this regard, it is of clinical interest to identify alternative
approaches that may confer key benefits of exercise with
enhanced participation and compliance in such groups.
The objective of this novel study was to test the efficacy
of WBVT on relatively new, but well-established biological
markers of CVD development and inflammation. Given the
current lack of understanding connecting the known benefits
of exercise and cardiovascular health, findings from this study
have strong potential to provide insight and direction to med-
ical therapies for numerous clinical conditions, particularly
in individuals with impaired activity levels. The goal of this
study was to test the hypothesis that WBVT would increase
the acute mobilization of peripheral blood stem/progenitor
cells and promote anti-inflammation when applied in subjects
without known cardiovascular risks as proof-of-concept.
METHODS
Study Protocol and Participants
This study was a single site (Indiana University Purdue Uni-
versity Indianapolis, IUPUI, Indianapolis, IN, USA), within
subjects, pre-, and post-test design. The protocol was approved
by the Institutional Review Board ethics committee of the
Indiana University School of Medicine a priori. A total of 11
subjects were enrolled and informed consent was obtained.
Exclusion criteria included known cardiovascular, pulmonary
or metabolic disease (eg, diabetes), current smoking or those
who quit within the previous 6 months, previous episode
of angina pectoris (chest discomfort), any orthopedic, mus-
culoskeletal or neuromuscular condition that would prohibit
moderate-intensity lower body resistance exercise, current
use of anti-hypertensive or anti-lipemic medications, regular
participation in aerobic physical activity (greater than or equal
to 3 days/week for greater than or equal to 30 min/day), or
recent (less than 6 months) participation in resistance training
exercise.
After prescreening, subjects were asked to refrain from
aerobic activity for 24 hour and to fast overnight prior to being
tested in the early morning (between 7 and 8 a.m.) since CPC
levels are known to be influenced by activity, food intake,
and time of day.21 Subjects remained seated 20 minutes prior
to testing to establish a common baseline. Heart rate (HR)
and BP readings were obtained, and peripheral venous blood
samples were drawn when the subjects were in the seated
position, pre- and post-activity at each session.
The participants were assigned to perform each of the
following three activities in random order on separate days:
(1) standing only on a vibrating platform (vx), (2) repetitive
leg squats exercise (sq) (no vibration), and (3) repetitive leg
squats exercise on a vibrating platform (vx and sq) (Fig. 1).
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Vibration Increases Circulating Stem Cell Levels
FIGURE 2. Representative gating strategy for flow cytometry characterization of peripheral blood MNC. Live cells are selected from the low side scatter
lymphocyte fraction, and populations phenotyped through a sequential gating strategy using FMO controls to help set gate boundaries. The strategy for
identifying the ECFC population is depicted here for illustration.
There was a gap of 4 to 7 days in between consecutive trials
over a period of 2 to 3 weeks.
All trials involving vibration were performed on the Power
Plate my3 (Power Plate North America, Northbrook, IL).
WBVT procedures were performed similar to other proto-
cols.18,22–24 The vibrations were set at 35 Hz with an ampli-
tude of 4 mm.
To ensure standardized foot placement, tracing paper was
marked during the first trial and used subsequently. All trials
were performed without shoes on and feet shoulder-width
apart. Subjects were allowed to use the vibration platform
handrails for balance as needed, but gripping was discouraged.
During standing only with vibration, each subject per-
formed a total of eight bouts (sets) on the vibration platform
for 60 s/bout. Subjects kept knees slightly bent to mini-
mize vibratory transmission to the head.25 Subjects rested for
120 seconds between bouts while seated.
During dynamic leg squats, both with and without vibra-
tion, subjects performed eight bouts, 60 s/bout, of leg squats
on the vibration platform or without vibration on the floor
(on separate days). Subjects squatted to 90◦knee flexion. A
metronome was used to pace each repetition at a rate of 15 rep-
etitions of leg squats per bout (120 repetitions total). Subject
carried an additional 15% of their body weight to increase load
bearing through their long bones by wearing a vest (Xvest,
Houston, TX). Subjects rested seated for 120 seconds between
bouts.
Repeat HR and BP readings were monitored during the
intervention. Post-activity peripheral venous blood samples
were drawn when seated within 5 to 10 minutes after
completion of the activity. Blood samples were used for a
complete blood count, and stem/progenitor cell and plasma
analysis.
Identication of CPCs
Polychromatic flow cytometry was used for determination
of CPCs using a validated procedure.26 Mononuclear cells
(MNC) were isolated using Ficoll-Paque Plus media per man-
ufacturer instructions. The cells were stained using the fol-
lowing antibodies: CD34-PE, AC133-APC, CD14-PE-Cy5.5,
CD45-aPC-AF750, CD31-FITC, CD235a-Vio, CD41a-Vio,
and LIVE/DEAD Vio. ‘Fluorescence minus one’ controls
were used as gating controls because of the difficulty in
distinguishing weakly fluorescent cells from large negative
populations. Additionally, singly stained BD CompBeads and
amine polymer microspheres were used for compensation
controls. Stained fixed MNC samples were acquired on a BD
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Vibration Increases Circulating Stem Cell Levels
LSRII flow cytometer equipped with a 405 nm violet laser,
488 nm blue laser, and 633 nm red laser. At least 1,000,000
events were acquired for each sample. Data were acquired
uncompensated, exported as FCS 3.0 files, and analyzed using
FlowJo software (software generated compensation matrix
applied). Stem/progenitor cells were evaluated from the lym-
phocyte gate (Fig. 2). Data are reported as total cells/mL
blood. The percentage of positive cells was converted to cells
per ml of blood using the complete blood count.
Cells types were identified based on the study by Estes
et al. 26 with some modifications, including: pro-angiogenic
CPCs; CD31+CD34brightCD45dim AC133+CD14−CD41a−
CD235a−LIVE/DEAD Violet−; non-angiogenic CPCs CD31+
CD34bright CD45dim AC133−CD14−CD41a−CD235a−LIVE/
DEAD Violet−; endothelial colony forming cells (ECFC)
CD31+CD34bright CD45−AC133−CD14−CD41a−CD235a−
LIVE/DEAD Violet−; MSC CD31−CD34brightCD45−CD14−
CD41a−CD235a−LIVE/DEAD Violet−; and hematopoietic
stem cells (HSC) CD34brightCD45+CD14−CD41a−CD235a−
LIVE/DEAD Violet−.
Cytokine Analysis
Plasma levels of VEGF, inflammatory (interleukin-6,
IL-6 and tumor necrosis factor-alpha, TNF-α), and anti-
inflammatory (interleukin-10, IL-10) cytokines were analyzed
using enzyme-linked immunosorbent assay kits following the
manufacturer’s instructions: VEGF (DVE00), IL-6 (DY206),
TNF-α(DY210), IL-10 (DY2178B) (R&D Systems, Min-
neapolis, MN). All samples from each participant were run
simultaneously, in duplicates.
Statistical Analysis
Statistical analysis was performed using FlowJo software.
Data were uncorrected. Graphpad Prism 7 was used for stats.
Pre- and post-exercise levels of cells and cytokines were
compared using the paired t-test. A value of P<0.05 was
considered significant. Quantitative data are represented as
mean ±SEM.
RESULTS
All individuals who were recruited completed the study.
Anthropometric characteristics of the subjects are presented
in Tabl e I . A younger sub-population had an average age of
24 years, although an older population was around 55 years.
Apart from age, there were no significant differences in height,
weight, or body mass index. Cardiovascular performance
findings in response to the different activities are summarized
in Tabl e I . Cardiovascular responses (BP and HR) did not
differ significantly between younger and older participants
during any activity. However, HR increased more with
squatting compared with vibration alone in both younger
and older individuals. The HR was measured and found to
be 69 ±2 beats/min before and 117 ±9 beats/min after
squatting (P=0.014) in the young group. In the older group,
TABLE I. Subject Characteristics and Cardiovascular Performance
Young
(n=6)
Old
(n=5)
Anthropometric characteristics
Age (year) 24 ±155±3∗
Height (m) 1.79 ±0.03 1.81 ±0.03
Weight (kg) 81 ±479±4
BMI (kg/m2)25±224±1
Cardiovascular performance
Pre-exercise resting HR (bpm) 69 ±269±1
HR during exercise protocol (bpm)
Vibration only 84 ±972±5
Squatting only 117 ±9#99 ±7#
Vibration with squatting 113 ±12#106 ±6#
Pre-exercise resting systolic BP (mmHg) 124 ±3 119 ±2
Systolic BP during activity (mmHg)
Vibration only 125 ±5 126 ±5
Squatting only 130 ±7 139 ±9
Vibration with squatting 136 ±8 130 ±6#
The only significant difference in subject characteristics was age. There was
a significant increase in HR from baseline (pre-exercise) with exercise alone
and with vibration plus exercise, but not with vibration alone. BP did not
vary significantly with activity except during combined activity in the older.
Values are means ±SEM.
∗Pvalues indicate statistically significant difference between old and young;
t-test, P<0.05.
#Statistical significance difference after exercise compared to baseline;
paired t-test, P<0.05.
it was 69 ±1 beats/min before and 99 ±7 beats/min after
squatting (P=0.02). In order to test the effects of the activities
on blood parameters, complete blood counts and differentials
were performed (Tabl e I I). Squatting alone had significant
effects on the white blood counts, blood parameters, and
differential populations, although vibration alone increased
hemoglobin and platelet counts, and combined activity only
increased neutrophil levels. Age was not an apparent factor.
Circulating Stem/Progenitor Cell Levels
Circulating CPC (CD31+CD34brightCD45dim ) levels increased
21% with repetitive leg squats, from 1465 ±202 to
1770 ±221 cells/mL (P=0.017), and approached sig-
nificance with vibration alone (1747 ±273–2091 ±414,
P=0.08). Sub-analysis revealed that vibration alone in
younger participants increased CPCs levels by 33% to a
level of significance (1918 ±341–2559 ±496, P=0.02).
Further consideration of CPC subsets, angiogenic (AC133+)
versus non-angiogenic (AC133−) was completed. Angiogenic
CPCs increased by nearly 34% from 504 ±102 to 674 ±152
cells/mL (P=0.04) in subjects who performed repetitive leg
squats with vibration; however, sub-analysis found this effect
only in the younger population, up by 39% (633 ±128–
882 ±181, P=0.05). Non-angiogenic CPCs increased 42%
(900 ±187–1283 ±271, P=0.04) with vibration alone
(P=0.04), but specifically in the younger (1181 ±222–
1677 ±342, P=0.04), not older subjects (P=0.53); however,
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Vibration Increases Circulating Stem Cell Levels
TABLE II. Baseline and Post-Activity Blood Parameters from Complete Blood Count
Vibration Squat Vibration +squat
Baseline Post Baseline Post Baseline Post
HGB 14.6 ±0.3 14.9 ±0.3∗14.7 ±0.3 15.2 ±0.3∗14.2 ±0.3 14.7 ±0.4
Hct, % 42.8 ±0.9 43.7 ±0.9 43.2 ±0.7 44.7 ±0.7∗41.9 ±0.9 43.5 ±0.9
RBC, 106/uL 4.8 ±0.1 4.9 ±0.1 4.8 ±0.1 5.0 ±0.1∗4.7 ±0.2 4.8 ±0.1
PLT, 103/uL 203.4 ±12.1 215.3 ±12.8∗211.6 ±14.2 227.4 ±14.9∗199.8 ±14.9 204.4 ±19.2
NE, 103/uL 2.5 ±0.2 2.7 ±0.2 2.8 ±0.2 3.4 ±0.3∗2.6 ±0.2 3.0 ±0.2∗
LY, 10 3/uL 1.8 ±0.2 1.7 ±0.1 1.8 ±0.2 2.0 ±0.2∗1.9 ±0.3 2.2 ±0.2
MO, 103/uL 0.4 ±0.0 0.5 ±0.0 0.4 ±0.0 0.5 ±0.0∗0.4 ±0.0 0.5 ±0.0
EO, 103/uL 0.2 ±0.0 0.2 ±0.0 0.2 ±0.0 0.2 ±0.0 0.2 ±0.0 0.2 ±0.0
BA, 103/uL 0.0 ±0.0 0.0 ±0.0 0.0 ±0.0 0.1 ±0.0 0.0 ±0.0 0.0 ±0.0
Squatting alone had significant effects on the white blood counts, blood parameters and differential populations, although vibration alone increased hemoglobin
and platelet counts, and combined activity only increased neutrophil levels. Age was not a factor.
Values are means ±SEM.
∗Statistical significant difference P<0.05, paired t-test.
repetitive leg squats increased this cell population by 32% in
older participants (801 ±251–1053 ±325, P=0.05). No
significant effects of vibration, exercise, or the combination
of the two were found on endothelial colony forming
cell, MSC, or HSC populations. Findings are summarized
in Figure 3.
Plasma Cytokine Levels
Three additional subjects were recruited for plasma cytokine
analysis (n=14). Enzyme-linked immunosorbent assay
results found TNF-αincreased significantly with vibration
only (P<0.01). IL-6 approached a significant drop during
vibration (P=0.056) and when vibration and exercise
were combined (P=0.09), but not with exercise alone.
Significantly higher levels of IL-10 were found with vibration
alone (P<0.03). VEGF levels were significantly higher
with vibration only (P<0.005). Age did not appear to have
different significant effects on cytokine levels in younger
versus older subjects. Findings are summarized in Figure 4.
DISCUSSION
The purpose of this study was to evaluate the effects of
WBVT on the release of stem/progenitor cells and selected
cytokines in healthy individuals as proof-of-concept. CPC
levels increased with exercise alone and approached signif-
icance with vibration alone for all subjects, but in younger
participants, reached significance with just vibration alone.
The CPCs were further characterized as either angiogenic
or non-angiogenic to gain additional insight. Angiogenic
CPCs increased during combined activity, but only in younger
subjects. Non-angiogenic CPCs increased with vibration
alone in younger subjects, but only with exercise alone in
older participants. Significant increases in TNF-α,VEGF,and
IL-10 only occurred during vibration alone, although IL-6
approached a significant drop with vibration alone, with no
difference detected with age. Activity did not significantly
alter circulating levels of other cell types (ECFC, MSC,
and HSC). Only exercise significantly elevated HR, and
none of the activities affected BP. Findings suggest WBVT
has the potential to positively influence vascular health
and inflammation, more in younger than older individuals.
Vibration protocols could augment exercise or serve as an
exercise surrogate, having important implication in military
health and regenerative rehabilitation.
Angiogenesis is the process of shaping new blood vessel
formation from pre-existing blood vessels. Pro-angiogenic
CPCs are associated with angiogenesis and improved vascular
health, whereas non-angiogenic are involved with mainte-
nance of vascular integrity.27,28 Bone-marrow-derived CPCs
were first identified in 1990s. Recent evidence suggests that
stem cells mobilize from the bone marrow into the peripheral
blood, differentiate into circulating EPCs, and home to sites
to contribute to de novo vessel formation.29 Around 0.015%
MNC in peripheral blood are CD34+cells. EPCs form 0.02%
of circulating MNC. A study found the average CD34+/KDR+
EPC number in peripheral blood of healthy controls were
2.48∧2/mL blood.30 In this current study, circulating CPCs
levels increased with repetitive leg squats and approached sig-
nificance with vibration alone. Only vibration in combination
with leg squatting exercise increased circulating levels of pro-
angiogenic CPCs, but only in younger not older participants.
Non-angiogenic CPC circulating levels increased with vibra-
tion alone in the younger, but with exercise alone in older
subjects. These outcomes could have positive implications in
the use of WBVT, not only for up-regulating angiogenesis
in states of tissue repair, but also for health promotion and
disease prevention.31,32 Understanding the mechanisms for
these effects requires further investigation, but the intensity
or type of physical stimulus need to mobilize specific cell
populations that appears to differ with age.
The inflammatory and healing process involves a cas-
cade of events with a complex interaction of cytokines that
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Vibration Increases Circulating Stem Cell Levels
FIGURE 3. CPC Levels. (A) CPCs increased significantly during squat exercise and approached significance with vibration alone for all subjects, but vibration
alone increased CPCs in younger individuals. More specifically, (B) Angiogenic CPCs increased with vibration and exercise, but with a significant effect in the
younger not older subjects. (C) Non-angiogenic CPCs increased with vibration alone in all and the young, but only with squat exercise in older participants.
No significant changes were detected in circulating levels of (D) ECFCs (depicted) with any activity, nor for HSC or MSC (not depicted).
is well documented.33,34 Trauma and disease are associated
with the release and intricate interaction of inflammatory
mediators.35,36 Interestingly, VEGF is secreted by EPCs and
plays an important role in blood vessel sprouting, working in
synergy with TNF-αand other molecules in the process of
angiogenesis and healing. TNF-αis able to promote angio-
genesis by inducing various proangiogenic factors.37,38 TNF-
αand IL-6 along with other cytokines are pro-inflammatory,
although IL-10 is anti-inflammatory.39,40 IL-6 regulates local
and systemic inflammatory response, elevated relative to the
degree of injury.40
In this study, vibration in combination exercise may have
a pro-angiogenic effect given the increase in pro-angiogenic
CPCs together with higher VEGF and TNF-αlevels found
during this activity. Vibration alone may also have positive
effects on the maintenance of vascular health as suggested by
elevated non-angiogenic CPCs levels. Vibration alone appears
to have an anti-inflammatory effect as evidenced by a trend
in decreased inflammatory marker (IL-6) and a significant
increase in anti-inflammatory marker (IL-10) levels. Curi-
ously, this possible anti-inflammatory effect was dampened
when combining vibration with exercise, in that the drop
in IL-6 did not approach significance and the increased IL-
10 levels was muted, suggesting there may be a threshold
for the optimal dose and/or combination of activities. Addi-
tional studies with assays to detect an array of factors are
needed to better assess the inflammatory profile of individuals
with various conditions and activity levels in response to
WBVT.
The effects of WBVT on vascular function are not
fully understood, however it is possible that WBVT like
other physical exercise, increases vascular shear stress,
resulting in increased nitric oxide (NO) production41 and
improved peripheral blood flow,42–45 and can provoke
muscle hypoxia,17 a key regulator of angiogenesis.46 Shear
stress is a primary stimulus for NO production leading
to blood vessel dilation.47,48 Constitutive NO synthases
include neuronal and endothelial (nNOS; eNOS). NO is
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Vibration Increases Circulating Stem Cell Levels
FIGURE 4. Plasma cytokine levels. (A) TNF-αincreased significantly with vibration (P<0.01). (B) IL-6 approached a significant drop during vibration
alone (P=0.056) and when vibration and exercise were combined (P=0.09). (C) IL-10 was higher with vibration alone (P<0.03). (D) VEGF levels were
significantly higher with vibration only (P<0.005). Age effects were not detected.
an important mediator of angiogenesis and is stimulated
by VEGF which together with eNOS play an important
role in vascular homeostasis.47 Inflammatory conditions
can decrease the availability of NO. However, exercise
can decrease upstream inflammatory mediator levels, for
example, IL1B, improving NO availability.49 Further study
is needed to better determine the underlying mechanisms of
WBVT.
WBVT is a nonpharmacological approach shown to have
therapeutic benefits, for example, increased bone mass,
reduced pain, and improved function, although the results
are mixed because of varying methodologies and other
factors.50,51 Vibration training alone may benefit individuals
who cannot tolerate higher activity levels, offering some
similar benefits to exercise without as much cardiovascular
demand. In this study, none of the activities had a significant
effect on BP. Repetitive leg squatting exercise resulted
in a significant increase in HR and increased circulating
WBC levels, whereas vibration alone did not. Another study
determining the effects of vertical WBVT on HR, mean
arterial pressure, femoral artery blood flow, and leg skin
temperature during exercise found that adding WBVT to
repeated semi-squats was not a significant cardiovascular
stressor.52 Vibration may offer a less aggressive means to
obtain stem/progenitor cell mobilization and alter cytokine
levels with positive therapeutic implications.
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Vibration Increases Circulating Stem Cell Levels
There are several limitations in this preliminary study. A
high inter-subject variability existed, thus a larger sample size
and tighter inclusion criteria are needed in future work. In
addition, only low intensity vibration treatment was adminis-
tered. Other types of vibration may have different outcomes.
Finally, the blood was only sampled at a single time point (5–
10 minutes post-activity). This time point might not be optimal
for detecting the maximum effect of the activities on CPC or
cytokine levels.
Future research should assess optimal data-collection time
points and dose-activity response. Larger sample sizes that
consider gender and age effects should be considered. A long-
term goal is to conduct studies that determine the viability of
WBVT as a treatment option in specific disease conditions
such as CVD, frailty, trauma victims in intensive care or criti-
cal care units, immobilized elderly, and many other conditions
that render individuals unable to participate fully in exercise
protocols.
Vibration alone or in combination with exercise may help
to mobilize non-angiogenic and angiogenic stem/progenitor
cells into circulation levels. It may also help to attenuate
inflammation. Although more research is needed, these pre-
liminary findings point to the potential usefulness of WBVT in
the promotion of health, and the prevention and management
of CVD and other conditions.
CONCLUSIONS
The benefits of exercise have long been determined, but when
this is not possible or difficult, such as is the case for some
warfighters with traumatic injuries or debilitating disease, it
becomes important to find other ways to gain similar effects.
Preliminary results from this study suggest vibration proto-
cols to augment exercise, or as an exercise surrogate, may
offer a viable treatment option to help attenuate inflammation
and increase stem/progenitor cell circulation levels associated
with vascular health and improved functional outcomes. Find-
ings have important implications in regenerative rehabilitation
and military research and health.
ACKNOWLEDGMENTS
The authors are thankful to Bruce Neff, Kelsey Rupert, and Dongni Feng for
assistance with data collection and sample processing. Yameena Jawed, Sam-
ple/data collection, data analysis (stem/progenitor cell) and interpretation,
project coordination, manuscript writing and editing. Eleni Beli, Stem/pro-
genitor cell data analysis and interpretation, manuscript writing and edit-
ing. Keith March, Co-Senior Author. Study design, technical lab support,
manuscript editing. Anthony Kaleth, Senior Author. Study design, manuscript
editing, equipment, funding support (internal grant). M. Terry Loghmani:
Corresponding Author, Sample/data collection, data analysis and interpreta-
tion, project coordination, manuscript writing and editing, funding support
(start-up funds).
FUNDING
This study was supported by internal funding.
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