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  IN THIS Article
 ::  Abstract
 ::  Sources of Prima...
 ::  Isolation of Pri...
 ::  Characterization...
 ::  Differentiation ...
 ::  Evaluating MSC P...
 ::  Conclusion
 ::  Acknowledgments
 ::  References
 ::  Article Figures

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REVIEW ARTICLE
Year : 2007  |  Volume : 53  |  Issue : 2  |  Page : 121-127

Adult mesenchymal stem cells: Differentiation potential and therapeutic applications


Wolfson Centre for Stem Cells, Tissue Engineering and Modelling ('STEM'), University of Nottingham, Nottingham NG7 2UH, United Kingdom

Date of Submission31-Oct-2006
Date of Decision19-Dec-2006
Date of Acceptance17-Jan-2007

Correspondence Address:
V Sottile
Wolfson Centre for Stem Cells, Tissue Engineering and Modelling ('STEM'), University of Nottingham, Nottingham NG7 2UH
United Kingdom
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DOI: 10.4103/0022-3859.32215

PMID: 17495381

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 :: Abstract 

Adult mesenchymal stem cells (MSCs) are a population of multipotent cells found primarily in the bone marrow. They have long been known to be capable of osteogenic, adipogenic and chondrogenic differentiation and are currently the subject of a number of trials to assess their potential use in the clinic. Recently, the plasticity of these cells has come under close scrutiny as it has been suggested that they may have a differentiation potential beyond the mesenchymal lineage. Myogenic and in particular cardiomyogenic potential has been shown in vitro . MSCs have also been shown to have the ability to form neural cells both in vitro and in vivo , although the molecular mechanisms underlying these apparent transdifferentiation events are yet to be elucidated. We describe here the cellular characteristics and differentiation potential of MSCs, which represent a promising stem cell population for future applications in regenerative medicine.


Keywords: Adipogenesis, chondrogenesis, mesenchymal stem cells, osteogenesis, regenerative medicine


How to cite this article:
Jackson L, Jones D R, Scotting P, Sottile V. Adult mesenchymal stem cells: Differentiation potential and therapeutic applications. J Postgrad Med 2007;53:121-7

How to cite this URL:
Jackson L, Jones D R, Scotting P, Sottile V. Adult mesenchymal stem cells: Differentiation potential and therapeutic applications. J Postgrad Med [serial online] 2007 [cited 2014 Oct 23];53:121-7. Available from: http://www.jpgmonline.com/text.asp?2007/53/2/121/32215


Adult stem cells' is the collective term used to describe postnatal stem cells which, as opposed to embryonic or fetal stem cells, persist throughout life and fulfill functions to repair or replace cells within certain tissues in response to traumatic events or natural cell turnover. Among tissues identified to harbor stem cells throughout postnatal life, bone marrow has been studied for many years as a source of both hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Mesenchymal stem cells reside in the stromal fraction of the bone marrow, which provides the cellular microenvironment supporting hematopoeisis. Mesenchymal stem cells were first described as bone-forming progenitors from the stromal fraction of rats by Friedenstein and Petrakova in 1966[1] and Friedenstein went on to pioneer in vitro culture methods for the isolation and differentiation of MSCs.[2] MSCs have subsequently been shown to differentiate into a number of mesenchymal cell types including osteoblasts, chondrocytes and adipocytes.[3]


 :: Sources of Primary MSCs Top


MSCs are typically isolated from the stromal fraction of adult bone marrow. In fresh bone marrow, MSCs account for only 0.01-0.0001% of nucleated marrow cells.[4],[5] Murine MSCs are classically obtained from the femurs and tibias of mice by flushing the marrow out of the bones with culture medium and transferring the resultant cell suspension in culture. Human MSCs can be similarly obtained from healthy volunteers by taking aspirates of bone marrow from the iliac crest and expanding on tissue-culture plastic.[6] Over recent years, MSC-like cells have also been identified in a number of different tissues.[2] Cells exhibiting MSC morphology and cellular characteristics have been isolated from adult peripheral blood,[7] adipose tissue,[8] skin tissue,[9] trabecular bone,[10] as well as fetal blood, liver, bone marrow[11] and lung.[12] Further MSC-like populations have been discovered in umbilical cord blood[13] and within the chorionic villi of the placenta.[14] Amniotic fluid has also been cited as a source of MSCs, with potential far-reaching implications for such areas as prenatal diagnosis and gene therapy.[15]


 :: Isolation of Primary MSCs Top


It is notable that, contrary to most biological systems, human MSCs are better characterized than animal MSCs. This is probably due to the fact that MSCs are easily isolated and expanded from adult human tissue collected from healthy volunteers. Mesenchymal stem cells have nevertheless been isolated from a number of other species. Along with human MSCs, the better characterized cultures are those of rat[16] and mouse[17] origin, although therapeutic potential in large animal models has been investigated with MSCs from horse,[18] cow,[19] pig,[20] dog,[21] sheep[22] and baboon.[23] Three main approaches have been described for the isolation of MSCs and can either be used independently or combined together to obtain a more homogeneous culture. The traditional isolation method relies on the fact that MSCs selectively adhere to plastic surfaces, whereas hematopoietic cells do not and can therefore be removed through medium changes.[24] Whilst this eliminates most contaminating cells, the remaining heterogeneity of the culture progressively decreases by serial passaging and after a number of passages the culture is enriched in the self-renewing fraction, the stem cells. Another published isolation protocol involves centrifugation over a Percoll gradient, which separates cell populations based on their density and allows the enrichment of nucleated cells.[4] However, both methods are quite nonspecific and an approach that is now increasingly being used, resorts to sorting of bone marrow populations by flow cytometry (FACS), based on MSC reactivity to a number of antibodies. This can either be achieved by positively selecting for expressed antigens or by a process of immunodepletion of cells expressing hematopoietic and/or other lineage antigens. For instance, antibodies against CD34, a surface marker found on hematopoietic cells, are frequently used to identify and remove nonmesenchymal cells from a marrow culture.[3] Since there is no single specific marker available to unequivocally identify the MSC, different groups have opted for a variety of marker combinations. MSCs appear relatively stable as primary cultures[25],[26] although spontaneous transformation events have been observed in long-term cultures.[27]


 :: Characterization of MSCs Top


Markers used by different groups to identify the MSC fraction from human bone marrow include, but are not limited to, CD13, CD29, CD31, CD44, CD54, CD63, CD73, CD105, CD106, CD140b, CD166 and Stro1.[3],[28],[29],[30],[31],[32] Comparisons of the various combinations used by different investigators show that the majority of subsets include either CD29, CD105 or both. We have established that over 95% of cells from the human MSC culture used in our lab express both CD29 and CD105 [Figure - 1]B. Although these markers have been used by various groups, there is still no general consensus on the optimal marker combination for MSCs. Some of this conjecture may be due to variations in sample origin, culture techniques and media composition among laboratories or differences in the age of the donors from which the MSCs were obtained and used for immunophenotyping. Because different antibody subsets are likely to selectively isolate slightly different cell types, comparison and evaluation of published data arising from different groups can be difficult. For instance, some groups report a degree of heterogeneity in their cultures after isolation and purification, with occasional description of a subset of small rounded cells among the more common fibroblast-like phenotype[33] [Figure - 1]A. This ambiguity begs the question of what MSCs are: do they purely represent the proliferating fibroblastic-like progenitors from the bone marrow stroma or do they include all cells capable of forming mesenchymal tissue? In the absence of a specific cell marker, MSCs may well incorporate a number of different cell populations all potentially variable in their phenotypic and growth characteristics, with mesenchymal differentiation as a common denominator.


 :: Differentiation Potential Top


MSCs are usually grown as a monolayer culture in medium typically containing 10% fetal calf serum at 37°C in a humid environment containing 5% CO 2 . As for many other adult stem cells, MSCs are traditionally considered to only be capable of differentiating into cell types of their own original lineage, i.e., mesenchymal derivatives. We and many other groups have shown MSCs to be capable of forming osteoblasts, chrondrocytes and adipocytes both in vitro[34] and in vivo .[35] The ability of clonally expanded cells to form these three distinct cell types remains the only reliable functional criterion available to identify the genuine MSC and distinguish it from preosteoblast, preadipocyte or prechondrocytic cells which each only give rise to one cell type.[36]

Osteogenic potential

Osteogenic differentiation of MSCs is induced in vitro by treating a monolayer culture with a pro-osteogenic cocktail. Standardly used differentiation medium consists of dexamethasone, ascorbic acid-2-phosphate and beta-glycerophosphate.[37] Mineralized deposits can appear after a week, but the treatment is often maintained for up to three weeks in order to maximize the number and size of mineralizing nodules. Additional calcium is also used to increase in vitro mineralization.[10] Early signs of osteogenesis include an increase in bone-specific alkaline phosphatase activity, which can be measured enzymatically.[38] At the end of the treatment, cells can be fixed and stained with either Alizarin-Red S solution[10] [Figure - 1]C or silver nitrate for von Kossa staining,[37] which highlight the calcium phosphate deposits. Quantitative measurements of mineral deposition can then be obtained by colorimetry.[10] Furthermore, osteogenic differentiation is accompanied by the expression of genes such as osterix, cbfa1, osteopontin, osteocalcin, bone sialoprotein,[39],[40] which can be monitored at the RNA and protein level.

Chondrogenic potential

Chondrogenic differentiation is traditionally achieved by first forcing aggregation of 200,000 to 300,000 MSCs in chondrogenic medium, in order to generate a micromass pellet culture. Common to most culture protocols is the presence of dexamethasone, ascorbic acid phosphate and ITS+ supplement, which consists of bovine insulin, transferrin, selenous acid, linoleic acid and bovine serum albumin.[10] Further additives to the medium include sodium pyruvate, proline, L-glutamine and TGF-beta1,[37],[41] a growth factor involved in chondrogenesis in vivo .[42] Over the period of treatment, there is an upregulation of chondrogenic markers such as collagen II, collagen XI, aggrecan, perlecan and syndecan.[19],[43] After two to three weeks in culture, micromass pellets can then be fixed and embedded for sectioning and subsequent staining with Safranin-O, Toluidine blue or Alcian blue to highlight acid mucopolysaccharides, glycosaminoglycans and proteoglycans respectively.[10],[37],[41]

Adipogenic potential

Formation of mature adipocytes occurs following treatment of MSCs with a medium supplemented with dexamethasone, isobutylmethylxanthine, insulin and a PPARgamma agonist such as BRL 49653[10] with twice weekly medium changes for three weeks. Alternatively, MSCs can be exposed to three cycles of a treatment which alternates three days of culture in induction medium followed by two days in maintenance medium.[37] In this instance, the induction medium contains indomethacin instead of BRL 49653 and the maintenance medium contains insulin. The appearance of adipocytes containing lipid-filled droplets can be demonstrated by staining with oil red O [Figure - 1]D and by RT-PCR detection of adipsin, aP2 and PPARgamma expression.[3],[44] Quantitative data can be obtained by enzymatic dosage of the Glycerol-3-phosphate dehydrogenase, a marker of the mature adipocyte.[45] Furthermore, an elegant technique developed by Gimble allows the quantitation of adipocytes by flow cytometry in a MSC culture stained with the lipophilic dye nile red.[46]

Myogenic potential

In recent years, the extent of MSC multipotency has been frequently discussed, with many authors suggesting that MSCs have a differentiation potential broader than initially thought. When treated with the demethylating agent 5-azacytidine, MSCs have been demonstrated to have the ability to form muscle cells.[47] Myogenic potential has also been observed in a xenogeneic in vitro model where human MSCs are co-cultured with murine skeletal myocytes.[48]

Furthermore, MSCs have been shown to form cardiomyocytes,[49] which is being pursued as a potential replacement for the scar tissue formed as a result of myocardial infarction. Murine MSCs were reported to start beating spontaneously two weeks after 5-azacytidine treatment as well as assuming a cardiomyocyte-like morphology. The cells displayed both sinus node-like and ventricular cell-like action potentials and the beating rate was increased by isoproterenol treatment and blocked by a beta1-selective blocker, thus exhibiting signs of physiological cardiomyogenic response. This differentiation was supported by expression of alpha1, alpha1B, alpha1D, beta1 and beta2 adrenergic and M1 and M2 muscarinic receptors.[49] In all cases of MSCs displaying myogenic potential in vivo ,[48],[50] it is not clear how much of this ability is due to de novo myogenesis and how much is due to cell fusion events with resident myoblasts.[51] Whatever the mechanism may be, MSCs appear to provide a positive contribution to areas of muscular or cardiac damage, with no observed detrimental side-effects.[14],[52]

Neural potential?

Perhaps most interesting are the recent reports that under certain conditions MSCs can be made to form neural cells. Most studies showing the formation of both neuronal and glial cells from MSCs have been carried out in vitro ,[53],[54] complemented in a few instances by in vivo data,[55],[56] although in many cases the possibility of cell fusion cannot be formally ruled out. There have been a number of different approaches reported to trigger this apparent transdifferentiation in vitro . Some groups have used chemical treatments such as DMSO,[23],[57] whilst others have opted for the use of growth factors such as fibroblast growth factor (FGF), neuronal growth factor (NGF) and epidermal growth factor (EGF).[53],[54],[58],[59] However, recent evidence suggests that early positive results obtained using DMSO-based protocols are unreliable, as the neural-like morphology and gene expression displayed by MSCs after treatment were in fact due to toxicity.[60],[61] Despite this setback, many other groups have reported the production of MSC-derived neurons, astrocytes,[62] oligodendrocytes[53] and Schwann cells[63] in vitro with varying degrees of efficiency. There is, however, an intense ongoing debate about the nature of these differentiation responses. Are they merely an artefact of the in vitro process or do they represent genuine neural potential from MSCs? As mentioned earlier, the multipotency of the MSC seems to be a fluid and evolving concept as novel culture conditions and differentiation treatments are being developed.


 :: Evaluating MSC Potential for Therapeutic Applications Top


An ideal source of adult stem cells?

The availability of autologous MSCs, which are easily accessible from patients, makes them a promising source of cells for many clinical applications in the evolving field of regenerative medicine. As well as providing the scaffolding (stromal) fraction of the bone marrow for HSCs to proliferate on, MSCs are thought to play a role in hematopoiesis itself.[4] MSCs have been shown to significantly improve hematopoietic recovery in patients receiving high-dose chemotherapy when compared with autologous blood stem cell transfusion alone.[64] Koc et al[64] co-infused culture-expanded MSCs with autologous blood stem cells in breast cancer patients and observed accelerated hematopoietic recovery.

Furthermore, MSCs represent an advantageous cell type for allogenic transplantation as evidence suggests that MSCs are immune-privileged, with low MHC I and no MHC II expression,[65] therefore reducing risks of rejection and complications for transplantation. In utero transplantation of human MSCs into sheep have shown that grafted cells could integrate into a variety of host tissues without any specific immune response.[66] MSCs have also been found to be immunosuppressive, through a mechanism thought to involve paracrine inhibition of T- and B-cell proliferation[67] (reviewed in[65]) and as such have been used in trials investigating their effects on autoimmune diseases and GVHD.[68],[69] Co-infusion of donor-derived MSCs together with HSCs has been shown to reduce the incidence and severity of GVHD in sibling allografts.[70] It was recently reported that a nine-year-old patient suffering from progressive severe GVHD that was unresponsive to classical therapy was treated with a MSC intravenous transplant from his mother and demonstrated a complete recovery.[68] The hypo-immunogenic properties of MSCs are considered by some to be sufficient to allow transplantation even between individuals who are not HLA-compatible.[71]

Applications for osteochondral repair

MSCs represent one of the few adult stem cell populations already in use in the clinic. MSCs are currently used to develop new therapies for a number of skeletal conditions. The osteogenic potential of MSCs has been utilized to treat cases of defective fracture healing, both alone and in combination with scaffolds to repair large bone defects with a high degree of success.[72] MSCs have also been used for cartilage repair. Autologous MSCs were expanded ex vivo , embedded in a collagen gel and re-implanted into areas of articular cartilage defect in osteoarthritis patients.[73] In this study, formation of hyaline cartilage-like tissue was improved in the experimental group compared to control. Although most applications for tissue repair involve local transplantation of MSCs to directly target the area of injury, systemic transplantation of MSCs has been in place for a long time in hematopoietic stem cell transplants. Recently, children suffering from osteogenesis imperfecta were treated systemically with allogenic MSCs. Transplanted MSCs were shown to migrate to the bone and produce collagen, thus providing a new and efficient route to alleviate the debilitating consequences of this genetic condition.[74]

Potential applications of MSCs for myocardiac repair

Current clinical trials are investigating the potential of MSCs for the treatment of myocardial infarction.[75] As previously discussed, a number of groups have reported MSC differentiation into cardiomyocytes in vitro . The current in vivo approach consists of injecting undifferentiated MSCs or whole bone marrow directly into the heart and, although the underlying mechanisms remains to be elucidated, significant improvement has been detected.[76],[77] The report by Chen et al[78] demonstrates a significant and sustained improvement in global left-ventricular ejection fraction, suggesting that MSC infusion triggers the formation of new cardiomyocytes and neoangiogenesis in the human heart.[79] It is still unclear whether MSCs act directly by in situ differentiation or fusion with resident myocytes[48] or indirectly through secretion of pro-myogenic factors promoting endogenous myocardial repair, such as VEGF and FGF.[80]

Therapeutic potential beyond mesenchymal lineages

The ability of MSCs to migrate to the site of injury has also been reported following transplantation in the brain. MSCs transplanted into rat striata were seen to migrate across the corpus callosum and populate the striatum, thalamic nuclei and substantia nigra of the 6-OHDA-lesioned hemisphere.[81] Untreated MSCs systemically infused into animals with damaged brain tissue have also been seen to migrate to the trauma site and improve recovery, although whether this is via secretion of neuroprotective factors or by differentiation into neural tissue remains unclear. Whilst it is not disputed that the MSCs appear to serve a positive role in recovery, there is debate as to whether the signs of differentiation observed in situ are genuine or merely a result of cell fusion with resident neural cells. More research is required to determine the reality and precise extent of MSC contribution in brain repair models as such results could have implications for neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease or traumatic events such as stroke or spinal cord injury. Although the adult brain contains populations of neural stem cells[82],[83] these are insufficient to replace the massive number of cells needed to treat these conditions. The critical question has been to identify a source of neural progenitor cells for transplantation. The potential use of fetal tissue or differentiated embryonic stem cells suffers limitations due to tissue availability, ethical issues or safety concerns. The identification of an adult population of cells such as MSCs, which can be easily obtained from autologous or donated marrow and can be cultured and manipulated ex vivo, would represent a significant breakthrough in the search for many applications in regenerative medicine.


 :: Conclusion Top


Mesenchymal stem cells represent a population of cells with the potential to contribute to future treatments for a wide range of acute or degenerative diseases. Significant progress has been made to identify the pharmacological and molecular pathways driving MSC differentiation towards mesenchymal derivatives in vitro and preliminary results indicate that MSCs could be used to generate neural derivatives. Much remains to be done in order to evaluate the physiological relevance of these early observations and to unravel the molecular mechanisms governing their differentiation in vivo . Applications currently under investigation for MSC-based therapies include musculoskeletal and cardiac repair, as well as genetic manipulation of MSCs for gene therapy strategies. Directed differentiation of autologous MSCs towards extra-mesenchymal lineages is an exciting and promising area of stem cell biology, with potential for the repair of tissues where resident stem cells are not accessible, such as the brain. MSCs thus represent an interesting and versatile population of adult stem cells demanding further molecular characterization and functional investigation. Future research will define the extent of their potential as an autologous and allogenic stem cell source for clinical application.


 :: Acknowledgments Top


We are grateful to Julie Swales and Dr. Adrian Robins for their expert advice on flow cytometry. LJ is funded by the University of Nottingham. VS is grateful to the Anne McLaren Fellowship scheme and the Alzheimer's Society for their support.

 
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53 The Use of Cellular Magnetic Resonance Imaging to Track the Fate of Iron-Labeled Multipotent Stromal Cells after Direct Transplantation in a Mouse Model of Spinal Cord Injury
Laura E. Gonzalez-Lara, Xiaoyun Xu, Klara Hofstetrova, Anna Pniak, Yuhua Chen, Catherine D. McFadden, Francisco M. Martinez-Santiesteban, Brian K. Rutt, Arthur Brown, Paula J. Foster
Molecular Imaging and Biology. 2010;
[VIEW]
54 Células madre y medicina regenerativa en urología, 1.a parte: generalidades, riñón, teste e incontinencia
T. Pastor-Navarro,L.M. Moratalla-Charcos,L. Bermell-Marco,M. Beamud-Cortés,J.M. Osca-García,M. Gil-Salom
Actas Urológicas Españolas. 2010; 34(6): 510
[Pubmed]
55 MEK/ERK and p38 MAPK regulate chondrogenesis of rat bone marrow mesenchymal stem cells through delicate interaction with TGF-β1/Smads pathway : MAPK and Smads in chondrogenesis
J. Li, Z. Zhao, J. Liu, N. Huang, D. Long, J. Wang, X. Li, Y. Liu
Cell Proliferation. 2010; 43(4): 333
[VIEW]
56 Stem cells and regenerative medicine in urology, part 1: General concepts, kidney, testis and urinary incontinence
T. Pastor-Navarro, L.M. Moratalla-Charcos, L. Bermell-Marco, M. Beamud-Cortés, J.M. Osca-García, M. Gil-Salom
Actas Urológicas Españolas (English Edition). 2010; 34(6): 510
[VIEW]
57 Cell-cell interaction promotes rat marrow stromal cell differentiation into endothelial cell via activation of TACE/TNF-α signaling
Xu, J., Liu, X., Chen, J., Zacharek, A., Cui, X., Savant-Bhonsale, S., Chopp, M., Liu, Z.
Cell Transplantation. 2010; 19(1): 43-53
[Pubmed]
58 Bio-released gold ions modulate expression of neuroprotective and hematopoietic factors after brain injury
Mie Østergaard Pedersen,Agnete Larsen,Meredin Stoltenberg,Milena Penkowa
Brain Research. 2010; 1307: 1
[Pubmed]
59 Ovine bone marrow mesenchymal stem cells: isolation and characterization of the cells and their osteogenic differentiation potential on embroidered and surface-modified polycaprolactone-co-lactide scaffolds
C. Rentsch, R. Hess, B. Rentsch, A. Hofmann, S. Manthey, D. Scharnweber, A. Biewener, H. Zwipp
In Vitro Cellular & Developmental Biology - Animal. 2010; 46(7): 624-634
[Pubmed]
60 Placenta-derived MSCs are partially immunogenic and less immunomodulatory than bone marrow-derived MSCs
H. Fazekasova, Robert Lechler, Kelly Langford, Giovanna Lombardi
Journal of Tissue Engineering and Regenerative Medicine. 2010; : n/a
[VIEW]
61 Bone marrow-derived angiogenic cells restore lung alveolar and vascular structure after neonatal hyperoxia in infant mice
Balasubramaniam, V., Ryan, S.L., Seedorf, G.J., Roth, E.V., Heumann, T.R., Yoder, M.C., Ingram, D.A., Abman, S.H.
American Journal of Physiology - Lung Cellular and Molecular Physiology. 2010; 298(3): L315-L323
[Pubmed]
62 Encapsulated human mesenchymal stem cells: A unique hypoimmunogenic platform for long-term cellular therapy
Goren, A., Dahan, N., Goren, E., Baruch, L., Machluf, M.
FASEB Journal. 2010; 24(1): 22-31
[Pubmed]
63 Gravity, a regulation factor in the differentiation of rat bone marrow mesenchymal stem cells
Huang, Y., Dai, Z.-Q., Ling, S.-K., Zhang, H.-Y., Wan, Y.-M., Li, Y.-H.
Journal of Biomedical Science. 2009; 16(1): Art no 87
[Pubmed]
64 Endothelial Differentiation of Amniotic Fluid–Derived Stem Cells: Synergism of Biochemical and Shear Force Stimuli
Ping Zhang, Jason Baxter, Kateki Vinod, Thomas N. Tulenko, Paul J. Di Muzio
Stem Cells and Development. 2009; 18(9): 1299-1308
[Pubmed]
65 Selection of CD271+ cells and human AB serum allows a Large expansion of mesenchymal stromal cells from human bone marrow
A. Poloni,G. Maurizi,V. Rosini,E. Mondini,S. Mancini,G. Discepoli,S. Biasio,G. Battaglini,S. Felicetti,E. Berardinelli,F. Serrani,P. Leoni
Cytotherapy. 2009; 11(2): 153
[Pubmed]
66 Mesenchymal stem cells for bone repair and metabolic bone diseases
Undale, A.H., Westendorf, J.J., Yaszemski, M.J., Khosla, S.
Mayo Clinic Proceedings. 2009; 84(10): 893-902
[Pubmed]
67 Osteogenic differentiation of human mesenchymal stem cells directed by extracellular matrix-mimicking ligands in a biomimetic self-assembled peptide amphiphile nanomatrix
Anderson, J.M., Kushwaha, M., Tambralli, A., Bellis, S.L., Camata, R.P., Jun, H.-W.
Biomacromolecules. 2009; 10(10): 2935-2944
[Pubmed]
68 Mesenchymal Stem Cells for Bone Repair and Metabolic Bone Diseases
Anita H. Undale,Jennifer J. Westendorf,Michael J. Yaszemski,Sundeep Khosla
Mayo Clinic Proceedings. 2009; 84(10): 893
[Pubmed]
69 Stem cell bioprocessing: fundamentals and principles
M. R Placzek,I-M. Chung,H. M Macedo,S. Ismail,T. Mortera Blanco,M. Lim,J. Min Cha,I. Fauzi,Y. Kang,D. C.L Yeo,C. Yip Joan Ma,J. M Polak,N. Panoskaltsis,A. Mantalaris
Journal of The Royal Society Interface. 2009; 6(32): 209
[Pubmed]
70 Mesenchymal Stem Cells: Emerging Therapy for Duchenne Muscular Dystrophy
Chad D. Markert,Anthony Atala,Jennifer K. Cann,George Christ,Mark Furth,Fabrisia Ambrosio,Martin K. Childers
PM&R. 2009; 1(6): 547
[Pubmed]
71 Stem cells and cell replacement therapy for Parkinsonæs disease
Sonntag, K.-C. and Simunovic, F. and Sanchez-Pernaute, R.
Journal of Neural Transmission, Supplementa. 2009; (73): 287-299
[Pubmed]
72 MRNA expression of connectin 43 and connectin 45 following transplantation of allogenic bone marrow mesenchymal stem cells in rats with acute myocardial infarction
Zhao, Y.-M. and Zhong, G.-Q. and Li, J.-Y. and He, Y. and Ke, H.-H. and Wang, D.-X.
Journal of Clinical Rehabilitative Tissue Engineering Research. 2009; 13(45): 8895-8900
[Pubmed]
73 Microcarrier cytodex3 culture technique for amplification of a large amount of adult bone marrow mesenchymal stem cells
Han, B.-S., Shen, B.-Y., Zhang, R., Wang, Z.-H., Du, Z.-Y., Cheng, D.-F., Shi, M.-M., (...), Peng, C.-H.
Journal of Clinical Rehabilitative Tissue Engineering Research. 2009; 13(10): 1996-2000
[Pubmed]
74 Research and application of mesenchymal stem cells in ophthalmology
Zhang, X., Zhao, G.-Q.
Journal of Clinical Rehabilitative Tissue Engineering Research. 2009; 13(6): 1151-1154
[Pubmed]
75 Analysis of primary human keratinocytes using polyclonal antibodies
Spichkina, O., Petrov, Yu.
Journal of Biological Sciences. 2009; 9(4): 292-301
[Pubmed]
76 Two-photon imaging and nanoprocessing of stem cells with sub-20 fs laser pulses
Uchugonova, A., Isemann, A., Bückle, R., Watanabe, W., König, K.
Proceedings of SPIE - The International Society for Optical Engineering. 2009; 7183(71831A)
[Pubmed]
77 Mesenchymal Stem Cells: Emerging Therapy for Duchenne Muscular Dystrophy
Markert, C.D., Atala, A., Cann, J.K., Christ, G., Furth, M., Ambrosio, F., Childers, M.K.
PM and R. 2009; 1(6): 547-559
[Pubmed]
78 Standard study on superparamagnetic iron oxide labeled bone marrow mesenchynal stem cells in vitro
Li, J., Niu, B., Zhang, H., Liu, B.-X., Yue, X.-H., Fan, C.-I., Li, H.-Q., (...), Zhang, D.
Journal of Clinical Rehabilitative Tissue Engineering Research. 2009; 13(19): 3633-3639
[Pubmed]
79 Migration of bone marrow-derived mesenchymal stem cells induced by tumor necrosis factor-α and its possible role in wound healing
Fu, X., Han, B., Cai, S., Lei, Y., Sun, T., Sheng, Z.
Wound Repair and Regeneration. 2009; 17(2): 185-191
[Pubmed]
80 Stem cell bioprocessing: fundamentals and principles
Placzek, M.R. and Chung, I.M. and Macedo, H.M. and Ismail, S. and Mortera Blanco, T. and Lim, M. and Cha, J.M. and Fauzi, I. and Kang, Y. and Yeo, D.C.L. and others
Journal of The Royal Society Interface. 2009; 6(32): 209-232
[Pubmed]
81 Selection of CD271+ cells and human AB serum allows a Large expansion of mesenchymal stromal cells from human bone marrow
Poloni, A. and Maurizi, G. and Rosini, V. and Mondini, E. and Mancini, S. and Discepoli, G. and Biasio, S. and Battaglini, G. and Felicetti, S. and Berardinelli, E. and others
Cytotherapy. 2009; 11(2): 153-162
[Pubmed]
82 Effects of growth factors on multipotent bone marrow mesenchymal stromal cells
Molchanova, E.A. and Payushina, O.V. and Starostin, V.I.
Biology Bulletin. 2008; 35(6): 555-570
[Pubmed]
83 Transplantation of Bone Marrow--Derived Mesenchymal Stem Cells Improves Diabetic Polyneuropathy in Rats
Shibata, T. and Naruse, K. and Kamiya, H. and Kozakae, M. and Kondo, M. and Yasuda, Y. and Nakamura, N. and Ota, K. and Tosaki, T. and Matsuki, T. and others
Diabetes. 2008; 57(11): 3099-3107
[Pubmed]
84 Extracellular matrix gel is necessary for in vitro cultivation of insulin producing cells from human umbilical cord blood derived mesenchymal stem cells
Feng, GAO and De-quan, WU and Yan-hua, HU and Guang-xin, JIN
Chinese Medical Journal. 2008; 121(9): 811-818
[Pubmed]
85 VLIYaNIE FAKTOROV ROSTA NA MULæTIPOTENTNYE MEZENKhIMNYE STROMALæNYE KLETKI KOSTNOGO MOZGA
Molchanova, EA and Payushina, OV and Starostin, VI
Izvestiya RAN. Seriya biologicheskaya. 2008; 6: 645-662
[Pubmed]
86 Cell therapies: realizing the potential of this new dimension to medical therapeutics
Singh P, Williams DJ
JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE. 2008; 2(6): 307-319
[Pubmed]
87 Natural Distribution and Principal Characteristics of Lupinus in the Oriental Face of Tlaloc Mountain in Sierra Nevada, Mexico
Angel Alderete-Chavez, Vicente Espinosa Hernandez, Enrique Ojeda Trejo, Muhammad Ehsan, Jesus Perez Moreno, Victor Manuel Cetina Alcala, Dante Arturo Rodriguez Trejo, Nancy De la Cruz-Landero
Journal of Biological Sciences. 2008; 8(3): 604
[VIEW]
88 Oxidative Stress and DNA Damage in Streptozotocin-Induced Diabetic Rats: Effects of Alpha Lipoic Acid
B. Siti Balkis, R. Nor Fadilah, A. Ezlan, O. Khairul, A.B. Mokhtar, M. Jamaludin
Journal of Biological Sciences. 2008; 8(3): 622
[VIEW]
89 Dissimilar differentiation of mesenchymal stem cells from bone marrow, umbilical cord blood, and adipose tissue
Rebelatto CK, Aguiar AM, Moretao MP, et al.
EXPERIMENTAL BIOLOGY AND MEDICINE. 2008; 233(7): 901-913
[Pubmed]
90 In vitro cultivation of islet-like cell clusters from human umbilical cord blood-derived mesenchymal stem cells
Gao F, Wu DQ, Hu YH, et al.
TRANSLATIONAL RESEARCH. 2008; 151(6): 293-302
[Pubmed]
91 Mesenchymal stem cells in tissue engineering
Godara P, Nordon RE, McFarland CD
JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY. 2008; 83(4): 397-407
[Pubmed]
92 Transplantation of bone marrow-derived mesenchymal stem cells improves diabetic polyneuropathy in rats
Shibata, T. and Naruse, K. and Kamiya, H. and Kozakae, M. and Kondo, M. and Yasuda, Y. and Nakamura, N. and Ota, K. and Tosaki, T. and Matsuki, T. and Nakashima, E. and Hamada, Y. and Oiso, Y. and Nakamura, J.
Diabetes. 2008; 57(11): 3099-3107
[Pubmed]
93 Immune effects of mesenchymal stem cells: Implications for Charcot-Marie-Tooth disease
Leal, A. and Ichim, T.E. and Marleau, A.M. and Lara, F. and Kaushal, S. and Riordan, N.H.
Cellular Immunology. 2008; 253(1-2): 11-15
[Pubmed]
94 Effects of growth factors on multipotent bone marrow mesenchymal stromal cells
E. A. Molchanova,O. V. Payushina,V. I. Starostin
Biology Bulletin. 2008; 35(6): 555
[Pubmed]
95 Optical knock out of stem cells with extremely ultrashort femtosecond laser pulses
Aisada Uchugonova,Andreas Isemann,Erwin Gorjup,Gabriel Tempea,Rainer Bückle,Wataru Watanabe,Karsten König
Journal of Biophotonics. 2008; 1(6): 463
[Pubmed]
96 Cell therapies: realizing the potential of this new dimension to medical therapeutics
Pawanbir Singh,David J. Williams
Journal of Tissue Engineering and Regenerative Medicine. 2008; 2(6): 307
[Pubmed]
97 Endothelial progenitor cells as targeted antitumor vectors for human gamma interferon gene
Wang, H., Liu, G., Song, S., Xu, J.
Chinese Journal of Clinical Oncology. 2008; 35(13): 761-765
[Pubmed]
98 Immune effects of mesenchymal stem cells: Implications for Charcot--Marie--Tooth disease
Leal, A. and Ichim, T.E. and Marleau, A.M. and Lara, F. and Kaushal, S. and Riordan, N.H.
Cellular Immunology. 2008; 253(1-2): 11-15
[Pubmed]
99 Immune effects of mesenchymal stem cells: Implications for Charcot–Marie–Tooth disease
Alejandro Leal, Thomas E. Ichim, Annette M. Marleau, Fabian Lara, Shalesh Kaushal, Neil H. Riordan
Cellular Immunology. 2008; 253(1-2): 11
[VIEW]
100 Engineering injured spinal cord with bone marrow-derived stem cells and hydrogel-based matrices: A glance at the state of the art
Perale, G., Bianco, F., Giordano, C., Matteoli, M., Masi, M., Cigada, A.
Journal of Applied Biomaterials and Biomechanics. 2008; 6(1): 1-8
[Pubmed]
101 Optical knock out of stem cells with extremely ultrashort femtosecond laser pulses
Uchugonova, A. and Isemann, A. and Gorjup, E. and Tempea, G. and Buckle, R. and Watanabe, W. and Konig, K.
Journal of Biophotonics. 2008; 1(6)
[Pubmed]
102 Biological characteristics of adult human marrow mesenchymal stem cells cultured in autoserum
Zhang, Y., Chen, L.M., Zhang, L., Ni, H.X.
Journal of Clinical Rehabilitative Tissue Engineering Research. 2007; 11(28): 5523-5526
[Pubmed]
103 Gene Expression Analyses of Human Mesenchymal Stem Cells Cultured in Osteogenic Differentiation Medium for 3, 7, 14 and 21 Days by Genome Focus DNA Microarray and Real-time PCR
TAIRA, M. and CHOSA, N. and SASAKI, K. and SAITOH, S. and NEZU, T. and SATO, N. and ARAKI, Y.
Journal of Oral Tissue Engineering. 2007; 5(1): 35-47
[Pubmed]



 

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Online since 12th February '04
© 2004 - Journal of Postgraduate Medicine
Official Publication of the Staff Society of the Seth GS Medical College and KEM Hospital, Mumbai, India
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