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Journal of Life Sciences and Technologies Vol. 1, No.

1, March 2013

Introducing a Novel Human Stem Cell with


Exceptional Characteristics: Small, Mobile Stem
Cells (SMS)
A. Rahmo, M. Elwi, M. Saleh and A. Almasri
National Commission for Biotechnology SYRIA
Email: a.rahmo@gmail.com


Abstract—Blood especially umbilical cord blood is a bone marrow. Using a multi donor UCB combined sample
valuable source of adult stem cells. These cells are quite is hampered by the probability of finding a suitable match
heterogeneous, and are far from being fully explored. We [1].
describe herein a novel cell population with extraordinary Cord blood cells have been successfully tested for ex
features. Long-term adherent cell culture was initiated and
vivo proliferation, and differentiation into cells of some,
characterized microscopically. Cell movement was measured
using suitable software. Flow cytometric measurements were or even all three germ layers; demonstrating their
used to characterize surface antigens. Standard multi-potent and pluripotent plasticity. Described cells
differentiation media were applied and histochemical include hematopoietic stem cells (HSC), mesenchymal
methods used to examine differentiation. Cultured cells stem cells (MSC), unrestricted somatic stem cells (USSC),
isolated from umbilical cord blood were very small, strongly endothelial colony forming cells (ECFC), and other stem
adherent, CD34+ cells. They proliferated for more than a cells that may be more primitive (cord blood derived
year in standard media without spontaneous differentiation, embryonic like stem cells CBE [2], very small embryonic
senescence or apoptosis, and displayed resistance to some like stem cells [3], multi lineage progenitor cells MLPC)
adverse conditions. These cells formed a complex
[4]. All these cells are relatively rare; and often the
extracellular matrix, and multi-cellular layers. They
exhibited exceptional kinetic characteristics with detected
isolation of a particular population fails. Their phenotypes
speed of 1.5 µm/sec. They are responsive to common vary in terms of structure (size, shape, antigens etc.) and
differentiation inductive media. Under these conditions, function (proliferative and differentiation potential,
clear changes to cell structure, and cell complex assembly, is sensitivity to media and environment, homing to tissues or
microscopically observed. This cell type is termed SMS organs etc.). Although some of UCB stem cells are
(Small, Mobile, Stem cell). Based on these exceptional relatively well defined, many are not [4] and this
features, we are confident that SMS cells will contribute represents the other main disadvantage of using UCB.
significantly to a new understanding and appreciation of Isolated stem cells may furnish interesting models for
human stem cells; ushering new venues for therapeutic and studying complex in vivo processes of tissue and organ
biotechnological applications.
genesis and repair. Moreover, defining the various stem
Index Terms—Cell differentiation, multilayer cell culture,
cells, in terms of their proliferative and plasticity potential
regenerative medicine, stem cells. and other characteristics, and achieving these potentials ex
vivo exact optimal stem cell population formulations. This
is a prerequisite for future medical translation into a wide
I. INTRODUCTION spectrum of therapy targets.
In the following we will present preliminary data on a
Umbilical cord blood (UCB) is a liquid tissue exposed cell line that has not been described earlier. This cell line
to many fetal organs and presents a heterogeneous displays a robust proliferative potential with multilayer
population of cells. UCB exhibits a higher ratio of stem formation, modest standard media requirements, growth
cells compared to peripheral blood. These also appear to potential in absence of serum, resistance to adverse
exact an intermediate status between embryonic stem cells environmental conditions, potential for high mobility, and
(ES) and adult stem cells (AS), in terms of their responsiveness to common differentiation inductive media.
proliferative potential, and spectrum of differentiations. The cells are termed SMS cells (Small, Mobile, Stem
UCB is used regularly as a bone marrow replacement. cells).
Many other applications are awaiting conclusion of
clinical trials despite inadequate preclinical studies [1]. II. MATERIALS AND METHODS
One main disadvantage of using UCB in tissue
regeneration relates to limited number of stem cells. UCB A. Sampling
is a onetime donation in contrast to, for example, adult
Human UCB was sampled postnatal from term delivery
umbilical cord of healthy mothers and babies. Samples
Manuscript received October 12, 2012; revised December 29, 2012.

©2013 Engineering and Technology Publishing 56


doi: 10.12720/jolst.1.1.56-61
Journal of Life Sciences and Technologies Vol. 1, No. 1, March 2013

obtained from volunteers were in accordance to E. Radiogenic Differentiation


institutional bioethical standards. The blood was collected Cells grown from UCB (passage 21 or greater), were
into a 250-mL standard blood collection bag (Baxter, sub cultured in growth medium 24 hours, and then grown
Deerfield, IL) containing citrate-phosphate-dextrose, and in adiposeness medium (growth medium plus: 1
was tested for bacterial or fungal contamination. The μmol/Ldexamethasone, 5 μg/mL insulin, 0.5 mmol/L
samples were processed within 24 hours of collection as isobutylmethylxanthine, and 60 μmol/L indomethacin) [6].
described. Half the medium was changed twice weekly. The media of
B. Cell Separation each flask were centrifuged. Collected pellets were
separately cultured at the same conditions using a tissue
Each 10 mL UCB sample was diluted with an equal
culture flat tube (TPP); representing the supernatant
volume of PBS. The diluted blood was layered over an
fraction.
equal volume of Ficoll-Paque (1.077 g/ml) (GE health
care Biosciences AB, Sweden). Mononuclear cells (MNCs) F. Neutrogena Cell Differentiation
were recovered from the gradient interface and washed Cells grown from UCB (passage 25 or greater) were
twice with PBS after centrifugation at 400 g for 30 min. seeded in T25 flasks (TPP). At 70% confluence, 1 mM
The layer of sediment red blood cells was also collected; it b-mercaptoethanol (BME) was added to growth medium
represented the RBC fraction. Cells positive for CD34 for 24 h. Cells were washed with D-Hanks buffer solution
were isolated from the MNC fraction, based on magnetic three times, and treated with 2% DMSO and 200 mM
micro bead selection procedure. High-gradient magnetic butyrate hydroxyanisole (BHA) in growth medium
field and MiniMACS (MS) columns were used (Miltenyi without FBS [7]. Cell morphology was observed using an
Biotech, Germany). eclipse TS100 (NIKON) inverted microscope and
C. Cell Culture and Cryopreservation photographed with a cyber shot (Sony) camera, in room
temperature. Cells were cultured further in the same flask
Cells from whole UCB mononuclear fraction and RBC
for several weeks, using the same inductive medium. Half
fraction were cultured separately and allowed to adhere to
the medium was replaced twice weekly.
the bottom of the T25 flask (Techno Plastic products TPP).
Culture was initially incubated in growth medium for four G. Histochemistry
days. Medium changes were carried out twice weekly Extracellular matrix was stained using the dye safranin
thereafter. Growth medium consists of Low-glucose (Merck). Cells were fixed using ice cold ethanol 70% for 1
Dulbecco’s Modified Eagle’s medium LG DMEM (Gibco) hour at room temperature, then stained with alizarin red S
with GlutaMAX™ and supplemented with 10% heat (Roth). Cells were fixed with 4% paraformaldehyde in
inactivated fetal bovine serum (FBS) (Invitrogen), 100 PBS for 30 - 60 min at room temperature, and treated with
U/mL penicillin, and 100 μg/mL streptomycin (Gibco) 60% isopropanol for 5 min, before staining with oil red O
incubated at 37°C and 5% CO2 in a humidified (Sigma). Cells were fixed with 4% paraformaldehyde in
atmosphere using the incubator (SHEL LAB, USA). At PBS for 30 - 60 min at room temperature and silver stained
later stages only half the medium was weekly changed. according to Bielschowsky [8].
Cells were usually passage upon reaching 80% to 90%
confluence using a scraper or cold shock treatment (~1h at H. Flow Cytometry Analysis
4-8 °C). All cell culturing manipulations were performed Cells were removed from culture flask using a scraper,
under strictly aseptic conditions in a dedicated class II and washed with PBS. Staining was with fluorescing
biosafety hood, using sterile single use plastic ware. A Try isothiocyanate (FITC), or phycoerythrin (PE)-conjugated
pan-blue dye exclusion test was used to distinguish the cell antibodies against CD10, CD13, CD14, CD15, CD34,
viability (Invitrogen). Cell number and viability were CD45, CD117, HLA-DR (BD PharMingen). The cells
estimated using the countess® cell counter (Invitrogen). forward and side scatter was measured, and cell surface
Cells were cryopreserved using a freezing medium staining was analyzed using a Becton Dickinson flow
consisting of 60% growth medium with 30% FBS and cytometer (Becton Dickinson, San Jose, CA).
10% DMSO.
I. Cell Movement Measurement
D. Osteogenic Differentiation Cultured cells were seeded in six well cell culture
Cells grown from UCB (passage 13 or greater), were clusters (TPP). Video images of cultured cells were
sub cultured in growth medium for 24 hours and then obtained using an eclipse 80i (NIKON) microscope
subjected to osteogenic medium (growth medium plus: 0.1 equipped with the Nikon coolpix 8800 camera, at 600x
μmol/L dexamethasone (Sigma), 0.05 mmol/L ascorbic magnification. Single cell movement was examined using
acid-2-phosphate (Sigma) and 10 mmol/L the software Tracker available for downloading at
β-glycerophosphate (Sigma)) [5]. Medium changes were [http//www.cabrillo.edu/~dbrown/tracker/]. The point
performed every 3 to 4 days. The media, containing mass representing a moving cell was tracked, and
detached cells and tissues of each flask, were centrifuged. distances were measured based on the calibration stick.
Collected pellets were separately cultured at the same Velocity was calculated based on video observed time
conditions, using a tissue culture flat tube (TPP); lapse.
representing the supernatant fraction.

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Journal of Life Sciences and Technologies Vol. 1, No. 1, March 2013

III. RESULTS growth medium. SMS cells were cultured successfully for
at least 60 days using the same growth medium without
A. Cell Isolation and Culture FBS. Absence of serum had no significant effect on
Whole UCB was used for culture after testing negative proliferation potential, shape or appearance. Cell
for bacterial or fungal contamination. The adherent separation using Ficoll density gradient centrifugation,
heterogeneous population of cells was observed on days: 4 indicated that SMS cells are enriched in the RBC layer.
and 5. Through continuous change of medium, the The same cells however have been also isolated from the
suspended cells became gradually fewer. Cells of various MNC layer; mainly as a CD34+ fraction.
shapes appeared at the bottom of culture flasks. The SMS B. Osteogenic Differentiation
cells were observed as very small sized adherent cells
(~5µm) with translucent cytoplasm, and a circular nucleus Following treatment with inductive medium, a fraction
(~3µm) that included what appears to be a very small of cells changed drastically their shape and size; becoming
circle of different contrast. Depending on focusing plane, larger and exhibiting standard cell morphology, with clear
the circle appeared darker or lighter. This, throughout cell nuclei and cytoplasma. A percentage of cells (~30%)
culture, stable shape of the minute cells appeared similar aggregated and tended to lessen attachment to surface.
to a human "Iris" (Fig. 1a). These cells were clearly Some aggregated cells formed assemblies of different
distinguished after 3-4 weeks from initiation. Cells with shapes, with or without color (Fig. 2a). A fraction of
the described appearance did not stain with any of the aggregated cells gained a clear orange color and formed a
standard Staining techniques (giemsa, methylene blue, complex assembly that became brownish (Fig. 2a). Many
papanicola, Wright) (Fig.1a). SMS cells strongly adhered of these, and some rather complex structures, were present
to plastic, and detachment using trypsin recipes was in the supernatant fraction (Fig. 2b). This differentiation
unsuccessful. Cells were therefore, dislodged using a medium induced apparently the formation of several
scraper or trough cold shock treatment. Primary culture different cell assemblies (Fig. 2d, e, and f). Many cells
cells reached confluence in 3-4 weeks. SMS cells were were stained strongly with the dye Alizarin Red S. Some
able to proliferate into a multilayer (at least three layers) of the complex assemblies of cells were also stained;
(Fig. 1b). Lower layer cells became attached more indicating accumulated calcium deposits (Fig. 2c). The
strongly to the surface of the flask through a layer of extra staining pattern was comparable to the one observed in a
cellular matrix (ECM). sheep bone control sample. Throughout culture, a large
At the bottom of the culture flask a dense mainly cell fraction of cells maintained the pre inductive shape of
free ECM layer appeared. Detaching portions of this layer SMS cells and continued to proliferate. Following six
from the flask by scraping made it floating; indicating a weeks of incubation with inductive medium, cells were
lower density than water. Further examination of this reincubated with the original growth medium. This caused
ECM indicated the actual presence of three disassembly of aggregated cells, and disappearance of
distinguishable sub-layers (Fig. 1c). The first was a some earlier formed complex structures (within ~2
smooth cell free layer in contact with the plastic of the weeks).
flask. The second was also a smooth layer. The third had a
rough surface containing some cells. The first and the
second layer were clearly distinctive due to differential
staining using the metachromatic dye safranin; the first
was stained yellow, the second red.

Figure 2 SMS cells derived from UCB cultured in estrogenic


differentiation medium. Assembly into complex structures; the adherent
fraction (a); the supernatant fraction (b). Structures, stained with alizarin
Red S (c). Various complex structures derived from the supernatant
Figure 1. Images of cultured SMS cells, derived from UCB, with typical fraction (d, e, f).
circular shape of the nucleus (~3µm) and the small dark circle in the exact
middle of the nucleus. The cytoplasm is hardly visible as a shadow (a).
SMS cultured multi-cellular layers appearing opaque (b). At the bottom C. Adipogenic Differentiation
of the flask; extracellular matrix made by in vitro cultured SMS cells, Inductive medium, caused many SMS cells to become
stained with safranin. The three arrows point to the distinctive three sub-
layers (c) larger; starting day 2, and some aggregated (Fig 3a). Some
cells appeared to accumulate lipid droplets of yellow color.
Continuous sub-culturing and long term culturing, out Oil Red O staining, demonstrated a rich lipid deposit in
selected other cells and homogenized the culture. Cells some cells. Aggregated cells formed multicellular
were continuously cultured, starting 11-2010 till 7-2012 assemblies with fat deposits (Fig. 3b). Many of these were
and further (27+ passages), with no apparent effect on present in the supernatant fraction (Fig. 3c). After 10 days,
proliferation potential. Cells were cryopreseved at flask inductive medium was replaced with the original
different passages and successfully revived in the same growth medium causing the former phenotype to

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Journal of Life Sciences and Technologies Vol. 1, No. 1, March 2013

disappear (2 weeks). Cells appeared to have reversed back absent or low granularity; consistent with the very
to the original pre-inductive morphology. translucent cytoplasm. Surface antigen analysis indicate
strong positivity for CD34, positive signals for CD10,
CD13, CD14, CD45, and negative signals for CD15,
CD117 (Fig. 5b, c).
F. Cell Movement
Figure 3. SMS cells derived from UCB; cultured in adipogenic Fast cellular movements were observed
differentiation medium. The shape of cells indicates drastic
morphological changes (a), assembly of cells into complex structures (b).
microscopically, real time, for some few cells; that is
Complex like structures, stained with Oil Red O (c). during normal cell culture conditions. Cell speeds of about
1.5 µm/sec were readily measured (Fig. 6). The type of
D. Neurogenic Differentiation this fast cell movement appeared similar to what is in
human movement characterized as "handspring"
Following treatment with β- Mercator ethanol no (acrobatic) movement. Fast cellular movements can be
visible changes were observed. After treatment with the induced, however, in almost the entire cell population by
second inductive medium, responsive cells (~60%) applying "adverse" cellular conditions (PH shock, cold
changed shape, became in some cases extended, and a chock, dislodging). Cellular movement was also observed
fraction of these cells became later thicker and refractile in cell cultures containing osteogenic inductive media. In
(Fig. 4a). Some cells became larger, but maintained an this case, whole clusters of cells appeared to be dragged by
approximate spherical shape. Both cells formed branches. single cells.
Some appeared multi polar, (Fig. 4a). Some cells have
their branches reaching to other cells and appeared to
IV. DISCUSSION
create intercellular contact (Fig. 4b). Some of the drastic
changes observed were within hours; while most appeared We have introduced a cell type that is phenotypically
the next day. Cells remained adherent to flask. Further quite distinguishable from earlier described cells. These
incubation with inductive medium at 37°C and 5% CO2 cells are very small in size, have a regular characteristic
for 30 days induced more significant changes to cell shape nuclear shape and a very translucent cytoplasm. These
and organization. Continuous cell growth and the cells are very fast in terms of mobility, but attach very
formation of multi-layers were observed, despite the strongly to plastic and very poorly to normal glass. They
absence of FBS in the neuronal inductive medium. do not stain with many standard staining techniques. The
Detaching induced cells and centrifugation resulted in a cells proliferate in standard media for more than 30
larger, clearly gray colored pellet, which was in contrast to passages, are quite resistant to adverse conditions, form a
the usual small white pellet of SMS cells; in absence of multilayer, excrete ECM, and can be grown in absence of
inductive media. Staining these cells indicated the serum.
presence of various argyrophilic cells, with a shape Once familiar with the peculiar phenotype of SMS cells,
characteristic to neuronal cells (Fig. 4d, e, and f). Some they became easy to isolate. The distinctive presences in
cells maintained SMS pre-inductive shape and continued sequential UCB samples, and the isolation from peripheral
to proliferate in the presence of inductive medium. At the blood, ensure their native origin. Easy reproduction of
bottom of the multilayer grown cells, a complex, dense, results, exclude the possibility of abnormal, transformed
mainly cell free layer appeared which constituted the ECM or mutated "flukes". Despite current intensive research on
attached to the base of the flask. Reversing post inductive stem cells, SMS cells appear to have eluded scientists.
cell shape by reincubating in growth medium was not Several factors might have contributed to this shortcoming:
observed in this case. the very small size of the cells, unstructured and
translucent cytoplasm, their mobility that could lead to
mistakenly identify the flask as infected, and eventually
cells, as bacterial contaminants, strong attachment to plate,
making cells cling to primary culture flask despite trypsin
treatment, exclusion of cell staining molecules, and the
presence away from ficol gradient layer of mononuclear
cells; usually opted for culturing.
Cell differential adhesion to plastic, or any other
Figure 4. SMS cells derived from UCB in cultured neurogenic
differentiation medium (a, b). Cell assembly (c) following early induction.
surfaces, can be considered as an important tool for
The shape of various silver stained cells appearing black or dark brown; isolating cells. The SMS cells attached strongly to plastic
consistent with neuronal silver staining (d, e). Assembly cells (f). after a flasks. According to manufacturer these flasks were
few weeks of induction. opto-mechanically activated by a process called corona
treatment. The process leads to a negatively charged
E. Flow Cytometric Analysis surface that is hydrophilic. The same flasks are usually
used by researchers to isolate MSC or USSC. However
Low forward scatter measurement values of tested
these cells were easily dislodged by trypsin treatment.
cultured SMS cells were obtained; consistent with its very
Other cells require different surface characteristics; the
small size (Fig. 5a). The low side scatter values indicated

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Journal of Life Sciences and Technologies Vol. 1, No. 1, March 2013

stem cell isolated by Zhao et al. adhered, for example, to topography and its physical characteristics are proven to
hydrophobic, positively charged, plastic surfaces [9]. be influential parameters. It is thought that at 3D culture
Recently a population of very small stem cells has been condition cellular gene expression would mirror more
isolated using FACS cell sorting [10]. Attempts to culture closely the in vivo state. Applications included the
these cells were unsuccessful, which led some researchers monitoring of tumor growth and metastasis, tissue
to question their very presence in human [11]. It is not engineering, and organ printing.
clear whether SMS cells are related to the elusive VSEL
cells, and this should be qualified. Both cell types share at
least the two features of small size and CD34 positivity.
Most adherent cells exhibit the phenotype of contact
inhibition preventing cells from further proliferating after
forming a confluent monolayer. Not so in SMS cells,
where the formation of multilayer’s was readily observed. Figure 5. Flow cytometric analysis of SMS cells: forward and side scatter
measurements (a). CD34 surface antigen measurements (b). CD14
This potential might be expected because some cells
surface antigen measurements(c).
remain mobile and are therefore able to initiate a new layer
on top of the completed earlier one. Plastic attachment is
obviously not necessary for forming a new cell layer.
Cancer cells are able to form multilayer’s too. They form
clusters and pile into mounds. Such structures, however,
are not readily observed in cultured SMS cells.
Interestingly, earlier research has demonstrated that
growing stem cells on surfaces that mimic ECM in vivo
may abolish contact inhibition of proliferation at
confluence [12]. The marked independence of SMS cells
from growth factors supplied by FBS, and its extensive Figure 6. The path of the moving SMS cell; tracked by the tracker
ability to establish an elaborate extracellular matrix software. The image includes single cells and cell clusters as pointed by
eliminating the need for pre-scaffolding, could be the white arrows. Upper right shows the plot diagram of movement time
relative to X coordinate position of the cell (circled).
accordingly of relevance for multilayer formation.
The characteristics of cell movements are important The extraordinary ability of SMS cells to establish
parameters that define specific cells. Cells vary, for organized ECM provides for an interesting model,
instance, considerably in their speed; fibroblasts move amenable to further exploration of these important aspects.
very These cells can also serve as a source of alternative ECMs;
Slowly (12-60 µm/h), while neutrophiles, thought to be enhancing henceforth studies of other cell lineages.
the fastest moving human cell, reach speeds of 30µm/min Most interesting is the fact that the effect of culturing
[13]. The results of this research were quite surprising, SMS cells in common inductive media was not limited to
since obtained speed values exceeded that of neutrophiles. actuation of cell differentiation, but was extended to a
This is, therefore, an important defining feature of SMS rallying of cells into assembly of various organized
cells. Cell movement is of particular importance to issues patterns. Some of which are reminiscent to what could be
of organogenesis, tissue repair and malignant cell invasion. found in adult tissues. Position sensitive and organized
Bone marrow derived cells have been shown to participate ECM secretion, and regular multi-cellular pattern
in tissue repair of several organs, including brain, liver, formation was observed during cell culture; especially in
lung, kidney and heart. Identification of BM derived cells, the presence of inductive media. Such complex patterning
in these injured tissues, suggests mobilization into would suggest multiple or extensive changes at gene
peripheral blood following organ stress communication. expression status; echoing the observed gross changes to
Interesting, in that context, was the observation of what individual cell architecture. The applied standard
appears as a collective cell movement. Such movement is inductive media resulted in a multitude of clearly
characterized by a cell cluster moving collectively; that is distinctive complex multi-cellular phenotypes. These
the SMS derived cells remaining in contact during observations outline the organo-genetic potency of SMS
movement. Collective movement is now widely cells.
recognized in embryogenesis and cancer [14]. SMS fast Stem cells present in adult tissue are considered to be
moving cells allow observation in short time intervals; in part of what is construed as an internal repair system for
which holding culture parameters constant is easily tissues. Asymmetric cell division ensures continuous
achieved. They could therefore serve as an important supply of proliferative and functionally differentiated cells
model, amenable for studying such complex tissue pattern [16]. Such asymmetry was observed in vitro in cultured
forming movements. SMS cells at all differentiation experiments; a fraction of
Three dimensional polymers mimicking ECM, as well cells appeared identical to cells prior to inductive exposure.
as reconstituted basement membrane, such as the Such asymmetry could likewise be postulated for mobility
commercial product Matrigel, have been shown to of cells; at standard conditions, only a fraction of cultured
promote cell organization and differentiation [15]. Matrix cells visibly move. Based on that perceived notion and the

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Journal of Life Sciences and Technologies Vol. 1, No. 1, March 2013

characteristics of SMS cells, a potential emergency tissue mesenchymal stem cells in vitro,‖ J Cell Biochem. vol. 64, no. 2, pp.
295-312, February 1997.
repair system can be hypothesized for SMS cells. Such a
[6] A. Erices, P. Conget, and J. J. Minguell, ―Mesenchymal progenitor
system would be served by a cell that is phenotypically: cells in human umbilical cord blood,‖ British Journal of
very small, exceptionally mobile, strongly yet reversibly Haematology vol. 109, no. 1, pp. 235–242, April 2000.
adherent, expressive of ECM, sensitive to environmental [7] X. Q. Kang, W. J. Zang, L. J. Bao, D. L. Li, X. L. Xu, and X. J. Yu,
changes yet resistant to adverse conditions, robust ―Differentiating characterization of human umbilical cord
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We think that we have presented an intriguing yet quite [8] D. S. der Achsencylinder, Neurologisches Zentralblatt, Leipzig,
amenable subject for further exploration. Having an ex 1902, vol. 21, pp. 579-584, Neurologisches Zentralblatt, Leipzig,
vivo continuously dividing stable stem cell line, issues the vol. 22, pp. 997-1006, 1903, Bielschowsky stains.
[9] Y. Zhao, Z. Huang, P. Lazzarini, Y. Wang, A. Di, and M. Chen, ―A
precondition for exhaustive and accurate assessment of unique human blood-derived cell population displays high potential
multilevel cellular phenotyping. The exceptional for producing insulin,‖ Biochem Biophys Res Commun. vol. 360, pp.
characteristics of this cell type assert clearly its novelty 205-211, June 2007.
among earlier described stem cells. Extensive flow [10] M. Kucia, M. Halasa, M. Wysoczynski, M. Baskiewicz-Masiuk, S.
Moldenhawer, E. Zuba-Surma et al., ―Morphological and molecular
cytometric analysis would complement its phenotypic characterization of novel population of CXCR4(+) SSEA-4(+)
description at antigenic level. Defining the gene Oct-4(+) very small embryonic-like cells purified from human cord
expression status would soon provide a molecular profile blood—preliminary report,‖ Leukemia, vol. 21, pp. 297-303,
that would make it particularly accessible to future February 2007.
[11] R. Danova-Alt1, A. Heider, D. Egger, M. Cross, and R. Alt, ―Very
biomedical manipulations. Current described small embryonic-like stem cells purified from umbilical cord blood
characteristics of SMS cells suggest moreover important lack stem cell characteristics,‖ PLoS one, vol. 7, no. 4, e34899,
future relevance to industrial biotechnological April 2012.
applications. If further, the expectation for the [12] H. Lu, T. Hoshiba, N. Kawazoe, I. Koda, M. Song, and G. Chen,
―Cultured cell-derived extracellular matrix scaffolds for tissue
involvement of SMS cells in tissue emergency repair is engineering,‖ Biomaterials vol. 32, vol. 36, pp. 9658-9666,
proven correct, any forthcoming studies could be of December 2011.
immediate regenerative benefit to many patients. In fact, [13] J. Persson, A. Mölder, S. G. Pettersson, and K. Alm, ―Cell motility
the presence of SMS cells in cord blood and their studies using digital holographic microscopy,‖ in Microscopy:
Science, Technology, Applications and Education. A.
persistent growth in absence of FBS, would simplify Méndez-Vilas, J. Dí az, Ed. Formatex 1063, ch 35, 2010.
eventually autologous transfer to this patients. [14] R. Mayor and C. Carmona-Fontaine, ―Keeping in touch with
contact inhibition of locomotion,‖ Trends Cell Biol. vol. 20, no. 6,
ACKNOWLEDGMENT pp. 319-328, June 2010.
[15] C. Gwendolen Reilly and A. J. Engler., ―Intrinsic extracellular
We would like to express our special gratitude to Mrs. matrix properties regulate stem cell differentiation,‖ Journal of
Inas Nemer, Ms. Hanan Al-Bast, and Ms. Banan al Shaikh Biomechanics, vol. 43, no. 1, pp, 55-62, January 2010.
[16] B. Giebel and I. Bruns, ―Self-renewal versus differentiation in
for their continuous and dedicated help during this hematopoietic stem and progenitor cells: A focus on asymmetric
research. None of the authors has any conflict of interest to cell divisions,‖ Current Stem Cell Research & Therapy, vol. 3, no. 1,
declare. pp. 9-16, January 2008.

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