Mesenchymal stem cells (MSCs) are multipotent stem cells which can support hematopoiesis, have immunomodulatory property, may differentiate into osteocytes, chondrocytes and adipocytes, and specifically migrate to damage sites and tumor site, but the mechanism involved in the regulation of migration of MSCs still remains unelucidated. Understanding the fundamental mechanisms underlying MSCs migration holds the promise of developing novel clinical strategies which can deliver antitumor proteins to suppress tumor growth. In this review, the MSC migration in vitro mediated by growth factors, chemokines, adhesion molecules and toll-like receptors are summarized.
Cell Movement ; physiology ; Humans ; Mesenchymal Stromal Cells ; cytology ; metabolism

Mesenchymal stem cells (MSC) have the capacities of low immunogenicity, multiple differentiation, hematopoietic supporting and immunoregulation. And due to their relative ease of availability and ex vivo expansion, the applications of MSC in the prevention and treatment of clinical disease have been rapidly expanded in the recent years. However, increasing investigations indicate that intravenously infused MSC widely distribute to various organs of the recipients. The two intended clinical goals of adoptive cellular therapy reached to the greatest efficiency. Therefore, the ideal candidate cells showed to have the capacity of site-specific relocation in vivo. In this review, the distribution characteristics of infused MSC and the recent research advances on the strategies to enhance targeted migration of MSCs are summarized.
Animals ; Cell Movement ; Humans ; Mesenchymal Stromal Cells ; cytology

OBJECTIVETo investigate the biological function of hepatocyte-like cells derived from mesenchymal stem cells that isolated from human umbilical cord UC-MSCs in vitro, and to detect the changes in the immunogenicity of the differentiated hepatocyte-like cells (DHC).

METHODSTransdifferentiation of UC-MSCs into hepatic lineage in vitro was induced in modified two-step induction medium. The expressions of hepatic specific markers were detected by RT-PCR analysis and immunofluorescence staining at different time points after induction. The levels of albumin and urea in the supernatants of cultures were measured by enzyme-linked immunosorbent assay. Furthermore, the immunosuppressive property of DHC was detected by one-way mixed lymphocyte culture.

RESULTSThe mRNA and proteins of alpha fetoprotein (AFP), albumin (ALB),and cytokeratin-19 (CK-19) were expressed in naive UC-MSCs at low levels. DHC highly expressed hepatic markers AFP, ALB, CK-19, and tryptophan 2, 3-dioxygenase 14 and 28 days after hepatic differentiation and were accompanied by an increased production of ALB and urea in supernatant in a time-dependent manner. DHC did not express human leukocyte antigen DR antigen and significantly decreased the lymphocyte proliferation.

CONCLUSIONUC-MSCs are able to differentiate into functional hepatocyte-like cells in vitro, while the immunogenicity of DHC remains low.

Cell Transdifferentiation ; Cells, Cultured ; Hepatocytes ; cytology ; immunology ; Humans ; Mesenchymal Stromal Cells ; cytology ; Umbilical Cord ; cytology

OBJECTIVETo investigate the possibility of transdifferentiation of adipose mesenchymal stem cells (AMSCs) into hepatocytes.

METHODSHuman omentum adipose tissue was dispersed with collagenase I. Cells collected were cultured in a DMEM-F12 medium containing 2% FBS supplemented with 20 ng/ml HGF, 10 ng/ml FGF4, 1xITS and 0.1 micromol/L dexasmison. The cells of the control group were also cultured in the same kind of medium but without any cytokines serving as a control. The expression of hepatic transcriptional factors such as GATA4 and HNF1 were checked by RT-PCR. At the end of the induction, hepatocyte markers were analysed by flow cytometry, and cytokeratin expressions were examined using cyto-immunofluorescence methods.

RESULTSAMSCs grew like fibroblasts and were passaged easily. Most of the third passaged AMSCs were positive against anti-CD29, anti-CD44 antibodies, but negative for the anti-CD34 and anti-CD45 ones. The hepatic transcriptional factor was expressed gradually to higher levels during the induction time. AFP and Alb positive cells were 30.0% and 17.8% of the total cultured cells, and the rate of cells positive to the two markers was 6.9%. The inducted cells were positive for CK18 and CK19 antibodies at the end of the induction. The cells in the control group were negative when checked by these methods.

CONCLUSIONSAMSCs could be directed to differentiate into hepatocytes in vitro by a cytokine cocktail with a low concentration FBS culture system.

Adipocytes ; cytology ; Cell Differentiation ; Cell Transdifferentiation ; Cells, Cultured ; Hepatocytes ; cytology ; Humans ; Mesenchymal Stromal Cells ; cytology

OBJECTIVETo review the in vitro development of bone marrow mesenchymal stem cells culture (BM-MSC).

DATA SOURCESThe data cited in this review were mainly obtained from articles listed in Medline and PubMed. The search terms were "bone marrow mesenchymal stem cell" and "cell culture".

STUDY SELECTIONArticles regarding the in vitro development of BM-MSCs culture, as well as the challenge of optimizing cell culture environment in two-dimensional (2D) vs. 3D.

RESULTSImproving the culture conditions increases the proliferation and reduces the differentiation. Optimal values for many culture parameters remain to be identified. Expansion of BM-MSCs under defined conditions remains challenging, including the development of optimal culture conditions for BMSC and large-volume production systems.

CONCLUSIONSExpansion of BM-MSCs under defined conditions remains challenges, including the development of optimal culture conditions for BMSC and scale-up to large-volume production systems. Optimal values for many culture parameters remain to be identified.

Animals ; Bone Marrow Cells ; cytology ; Cell Culture Techniques ; methods ; Cells, Cultured ; Humans ; Mesenchymal Stromal Cells ; cytology

Atherosclerosis is an inflammatory disease. However, its etiology has not been yet fully elucidated. Endothelial dysfunction is currently considered to be one of the most important steps in the initiation of atherosclerosis. In addition, vascular smooth muscle cells, which are the main cellular component of de novo and in-stent restenosis lesions, play an important role in the development of atherosclerosis. Promoting the regeneration of endothelial cells and inhibiting the proliferation of smooth muscle cells are pivotal for the prevention and treatment of vascular injury. Recently, some studies have demonstrated that mesenchymal stem cells can home to the site of injury and differentiate into endothelial cells to repair damaged blood vessels. On the contrary, other researches have revealed that mesenchymal stem cells can differentiate into vascular smooth muscle cells that are involved in the development of restenosis. Here, we review the fundamental researches of mesenchymal stem cell therapy for atherosclerosis and address the perspectives of mesenchymal stem cells in atherosclerosis treatment.
Animals ; Atherosclerosis ; therapy ; Cell Differentiation ; Cells, Cultured ; Endothelial Cells ; cytology ; Humans ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; cytology

This study was purposed to investigate the influence of inflammatory microenvironment on mesenchymal stem cells (MSCs) and regulatory effect of MSCs on osteoblast formation. The MSCs were isolated from synovial fluid of patients with rheumatoid arthritis (RASF-MSCs) and were cultured, the immunotypes of RASF-MSCs were detected by flow cytometry, the ability to differentiate RASF-MSCs into osteoblasts and adipocytes was determined by means of osteogenic and adipogenic induction, the regulatory effect of RASF-MSCs on osteoblast formation was assayed by co-culturing RASF-MSCs whth CD14(+) monocytes and in situ tartrate-resistant acid phosphatase staining. The results showed that RASF-MSCs highly expressed CD105, CD73, CD29, CD44, CD166 and HLA-ABC. Meanwhile, they lowly expressed CD34, CD45, CD31, HLA-DR, CD80 and CD86. However, RASF-MSCs decreased multi-differentiation capability as compared with BM-MSCs. More interestingly, RASF-MSC significantly promoted osteoclasts formation (p < 0.05) when co-cultured with monocytes. It is concluded that MSCs from rheumatoid arthritis synovial fluid exert typical MSC phenotypes but displayed decline of multi-differentiation capability. RASF-MSCs especially show promoting effect on osteoclastogenesis. The findings of this study may contribute to the understanding biological behavior of MSCs in pathological microenvironment.
Arthritis, Rheumatoid ; Bone Marrow Cells ; cytology ; Cell Differentiation ; Cells, Cultured ; Humans ; Mesenchymal Stromal Cells ; cytology ; Osteoblasts ; cytology ; Synovial Fluid ; cytology

Strong proliferative capacity and the ability to differentiate into the derivative cell types of three embryonic germ layers are the two important characteristics of embryonic stem cells. To study whether the mesenchymal stem cells from human fetal bone marrow (hfBM-MSCs) possess these embryonic stem cell-like biological characteristics, hfBM-MSCs were isolated from bone barrows and further purified according to the different adherence of different kinds of cells to the wall of culture flask. The cell cycle of hfBM-MSCs and MSC-specific surface markers such as CD29, CD44, etc were identified using flow cytometry. The expressions of human telomerase reverse transcriptase (hTERT), the embryonic stem cell-specific antigens, such as Oct4 and SSEA-4 were detected with immunocytochemistry at the protein level and were also tested by RT-PCR at the mRNA level. Then, hfBM-MSCs were induced to differentiate toward neuron cells, adipose cells, and islet B cells under certain conditions. It was found that 92.3% passage-4 hfBM-MSCs and 96.1% passage-5 hfBM-MSCs were at G(0)/G(1) phase respectively. hfBM-MSCs expressed CD44, CD106 and adhesion molecule CD29, but not antigens of hematopoietic cells CD34 and CD45, and almost not antigens related to graft-versus-host disease (GVHD), such as HLA-DR, CD40 and CD80. hfBM-MSCs expressed the embryonic stem cell-specific antigens such as Oct4, SSEA-4, and also hTERT. Exposure of these cells to various inductive agents resulted in morphological changes towards neuron-like cells, adipose-like cells, and islet B-like cells and they were tested to be positive for related characteristic markers. These results suggest that there are plenty of MSCs in human fetal bone marrow, and hfBM-MSCs possess the embryonic stem cell-like biological characteristics, moreover, they have a lower immunogenic nature. Thus, hfBM-MSCs provide an ideal source for tissue engineering and cellular therapeutics.
Bone Marrow Cells ; cytology ; Cell Proliferation ; Embryonic Stem Cells ; cytology ; Fetus ; Germ Layers ; cytology ; Humans ; Mesenchymal Stromal Cells ; cytology

Adult stem cells are drawing more and more attention due to the potential application in degenerative medicine without posing any moral problem. There is growing evidence showing that the human amnion contains various types of adult stem cell. Since amniotic tissue is readily available, it has the potential to be an important source of regenerative medicine material. In this study we tried to find multipotent adult stem cells in human amnion. We isolated stem cells from amniotic mesenchymal cells by limiting dilution assay. Similar to bone marrow derived mesenchymal stem cells, these cells displayed a fibroblast like appearance. They were positive for CD105, CD29, CD44, negative for haematopoietic (GlyA, CD31, CD34, CD45) and epithelial cell (pan-CK) markers. These stem cells had the potential to differentiate not only into osteogenic, adipogenic and endothelial lineages, but also hepatocyte-like cells and neural cells at the single-cell level depending on the culture conditions. They had the capacity for self-renewal and multilineage differentiation even after being expanded for more than 30 population doublings in vitro. So they may be an ideal stem cell source for inherited or degenerative diseases treatment.
Adult Stem Cells ; cytology ; Amnion ; cytology ; Cell Differentiation ; physiology ; Humans ; Mesenchymal Stromal Cells ; cytology ; Multipotent Stem Cells ; cytology

Bone marrow mensenchymal stem cells (BM-MSCs) are capable of supporting the survival, differentiation and migration of hematopoietic stem cell, and have a profound application prospect in transplantation and treatment of graft-versus-host disease (GVHD). This review aims to illustrate the interaction between BM-MSCs and other intra-bone marrow cells, including hematopoietic stem cells, endothelial cells and osteoblasts. The investigation of their regulating mechanism will help better understanding of the BM-MSCs' role in hematopoiesis.
Bone Marrow Cells ; cytology ; Cell Communication ; physiology ; Endothelial Cells ; cytology ; Humans ; Mesenchymal Stromal Cells ; cytology ; Osteoblasts ; cytology