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Frontiers of Medicine

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Front Med    2011, Vol. 5 Issue (4) : 372-378    https://doi.org/10.1007/s11684-011-0164-4
REVIEW
Mesenchymal stem cells hold promise for regenerative medicine
Shihua Wang, Xuebin Qu, Robert Chunhua Zhao()
Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
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Abstract

Regenerative medicine is an emerging interdisciplinary field of research that uses several technological approaches including stem cells to repair tissues. Mesenchymal stem cells (MSCs), a type of adult stem cell, have generated a great amount of interest over the past decade in this field. Numerous studies have explored the role of MSCs in tissue repair and modulation of allogeneic immune responses. The mechanisms through which MSCs exert their therapeutic potential rely on some key properties of the cells as follows: the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, cardiomyocytes, hepatocytes, endothelial, and neuronal cells; the ability to secrete multiple bioactive molecules capable of stimulating the recovery of injured cells and inhibiting inflammation; the lack of immunogenicity; and the ability to perform immunomodulatory functions. In the present review, we focus on these three aspects upon which the therapeutic effects of MSCs are mainly based. Furthermore, some pathological conditions under which the application of MSCs should be done with caution are also mentioned.
Keywords mesenchymal stem cells      differentiation      immunomodulation      regenerative medicine     
Corresponding Author(s): Zhao Robert Chunhua,Email:chunhuaz@public.tpt.tj.cn   
Issue Date: 05 December 2011
 Cite this article:   
Shihua Wang,Xuebin Qu,Robert Chunhua Zhao. Mesenchymal stem cells hold promise for regenerative medicine[J]. Front Med, 2011, 5(4): 372-378.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-011-0164-4
https://academic.hep.com.cn/fmd/EN/Y2011/V5/I4/372
TissueCell types producedReference
Term placental membranesAll embryonic germ layers, including alveolar type II cells[10]
Wharton's jelly of umbilical cordEctoderm-, mesoderm-, and endoderm-derived cells, including insulin-producing cells[11]
Amniotic fluidAll embryonic germ layers, including neuronal lineage cells secreting the neurotransmitter L-glutamate or expressing G-protein-gated inwardly rectifying potassium channels, hepatic lineage cells producing urea, and osteogenic lineage cells forming tissue-engineered bone[12]
Placenta and bone marrowAdipocytes and osteoblast-like cells (mesoderm), glucagon and insulin expressing pancreatic-like cells (endoderm), as well as cells expressing the neuronal markers neuron-specific enolase, glutamic acid decarboxylase-67 (GAD), or class III beta-tubulin, and the astrocyte marker glial fibrillary acidic protein (ectoderm)[13]
Human term placentaAll three germ layers—endoderm (liver, pancreas), mesoderm (cardiomyocyte), and ectoderm (neural cells) in vitro[14]
Placental cord bloodIn vitro—osteoblasts, chondroblasts, adipocytes, and hematopoietic and neural cells including astrocytes and neurons that express neurofilament, sodium channel protein, and various neurotransmitter phenotypes. In vivo—mesodermal and endodermal lineages demonstrated in animal models[15]
Adult bone marrowCells with visceral mesoderm, neuroectoderm, and endoderm characteristics in vitro[16]
Tab.1  Studies confirming the subtotipotent stem cell hypothesis
Disease modelDetailed informationReference
Lung injury—the thoraxes of C57BL/6 mice were exposed to 1 400 cGyMSCs injected immediately after injury were shown to differentiate into functional lung cells, such as epithelial and endothelial cells[20]
Hindlimb ischemia mouse modelMSCs differentiated in response to local cues into endothelial cells and contributed to neoangiogenesis[21]
Fibrosis formation induced by carbon tetrachloride (CCl4)MSCs engrafted into host liver, had epithelium-like morphology, and expressed albumin, although at a low frequency[22]
Lethally irradiated C57BL/6 miceFluorescence-labeled Flk + MSC of BALB/c mice (H-2Kd, white) were transplanted into lethally irradiated C57BL/6 mice (H-2Kb, black); donor cells could migrate and take residency at the skin. The recipient mice grew white hairs after approximately 40 days. Immunochemistry staining and RT-PCR demonstrated that skin tissue within the white hair regions was largely composed of donor-derived H-2Kd cells, including stem cells and committed cells. Furthermore, most skin cells cultured from white hair skin originated from the donor. Thus, these findings provide direct evidence that bone marrow-derived cells can give rise to functional skin cells and regenerate skin tissue[23]
Tab.2  Examples of MSCs used to treat diseases through differentiation
Bioactive moleculesFunctionsReference
Prostaglandin E2 Anti-proliferative mediators[24]
Interleukin-10Anti-inflammatory[25,26]
Transforming growth factor ?-1, hepatocyte growth factorSuppress T-lymphocyte proliferation[27]
Interleukin-1 receptor antagonistAnti-inflammatory[28]
Human leukocyte antigen G isoformAnti-proliferative for naive T cells[29,30]
LL-37Anti-microbial peptide and reduce inflammation[31,32]
Endothelial growth factor, basic fibroblast growth factor, placental growth factor, and monocyte chemoattractant protein-1Enhance proliferation of endothelial cells and smooth muscle cells[33,34]
Tab.3  Bioactive molecules secreted by MSCs and their functions
Fig.1  The immunomodulatory effects of MSCs both and .
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