Mesenchymal stem cells (MSC) have attracted high attention to their various origins, capability of multi-lineage differentiation, supporting hematopoiesis and regulating immunity. Consequently, MSC show great potential for tissue engineering and cell/gene therapy. The bone marrow microenvironment plays an important role in the pathogenesis of several hematological malignancies. It was confirmed that as key components of the hematopoietic microenvironment, MSC correlated complexly with tumor microenvironment. Recent reports showed that MSC from some patients with AML, MDS, ALL and MM harboured cytogenetic alterations. In addition, the phenotype, ability of differentiation and immunoregulatory function of MSC displayed different degree of abnormalities, suggesting that MSC played a role in the pathophysiological mechanism of malignant hematopoietic diseases. Besides, MSC have been found to participate in drug resistance of antileukemic therapy. Hematopoietic stem cell transplantation (HSCT) has become an important treatment approach for the malignant hematopoietic diseases in recent years. Because of the advantages of supporting hematopoiesis and regulating immunity, MSC are used to promote the engraftment and prophylaxis/treatment of GVHD. This review summarized briefly the abnormalities of mesenchymal stem cells in malignant hematological diseases and MSC research advances on cell therapy.
Bone Marrow Cells ; pathology ; Hematologic Neoplasms ; pathology ; therapy ; Humans ; Mesenchymal Stromal Cells ; cytology ; pathology

OBJECTIVETo compared the biological characteristics of adipose-derived stem cells and lipoma-derived mesenchymal stem cells (LMSCs) in vitro, so as to assess the safety of adipose-derived stem cells( ASCs) for transplantation.

METHODSRegular slice and stain of adipose and lipoma tissue were performed. ASCs and LMSCs were isolation from the two tissues by enzymatic digestion, and the appearance of the cultured cells was observed. The cell viability was evaluated with MTS chromatometry and cell growth curve was generated. Flow cytometry was performed for cell cycle analysis and the expression of the cell surface marker profiles. QRT-PCR was used to detect the expression of tumor-specific gene (the high-mobility group AT-hook 2, HMGA2), and immunocytochemistry was used to detect the expression of telomerase.

RESULTSMarked difference was observed in histologic sections of adipose tissue and lipoma tissue. ASCs showed a good consistent in cell morphology while LMSCs not. ASCs showed a significant lower proliferation capacity than LMSCs by MTS chromatometry (P = 0.000). The expression of CD29, CD44, CD105 was similar in ASCs and LMSCs, while the level of CD133 was significantly lower in ASCs (5.35%) than in LMSCs (26.87%). The expression of HMGA2 was lower in ASCs (RQ = 1) than in LMSCs (RQ = 1.79) by qRT-PCR, it has statistically difference between them (P < 0.01); And in ASCs and LMSCs, the integrated optical intensity (IA) values of hTERT expression are 1379.597 +/- 498.617 and 3 328.108 +/- 902.856, size (area) are 132,390.27 +/- 35,568.945 and 238,000.53 +/- 49,264.289, density (mean) are 0.009 +/- 0.003 and 0.014 +/- 0.003, revealed the expression of hTERT also shown a significant lower level in ASCs than in LMSCs by immunocytochemistry.

CONCLUSIONSIt indicates significant difference between ASCs and LMSCs in the biological characteristics in vitro. There is no evidence of malignant transformation of ASCs.

Adipose Tissue ; cytology ; Adult ; Cells, Cultured ; Humans ; Lipoma ; pathology ; Male ; Mesenchymal Stromal Cells ; cytology ; Stem Cells ; cytology

This study was aimed to compare the influences of bone marrow mesenchymal stem cells (BMMSCs) from patients with acute myeloid leukemia (AML), AML patients with complete remission (CR) and non-leukemia patients on HL-60 cells. The HL-60 cells were divided into three groups: group of co-cultivation with BMMSCs of AML patients, group of co-cultivation with BMMSCs of AML patients with CR and group of co-cultivation with BMMSCs of non-leukemia patients. The count of HL-60 cells, the CD11b and survivin expression of HL-60 cells, the cell cycle distribution of the HL-60 cells in 3 groups were compared by flow cytometry, the morphology and differentiation rate of HL-60 cells in 3 groups were observed and compared by microscopy. The results showed that there were no differences in HL-60 cell count at five and seven days, in HL-60 distribution at the G(0)/G(1) phase, in survivin and CD 11b expressions in 3 groups. All cells of 3 groups began to mature, and the differentiation rates in 3 groups were 18.0 +/- 3, 17.0 +/- 1.3 and 19.0 +/- 2.0 respectively, therefore there were no significant differences between the 3 groups (p = 0.23). It is concluded that there is no influence of BMMSCs in 3 groups on the proliferation and differentiation of HL-60 cells.
Bone Marrow Cells ; cytology ; Cell Differentiation ; Cell Proliferation ; Coculture Techniques ; HL-60 Cells ; Humans ; Leukemia ; pathology ; Mesenchymal Stromal Cells ; cytology

OBJECTIVETo investigate the effect of mesenchymal stem cell (MSC) transplantation in repairing ovarian injury in mice sensitized with porcine ovarian proteins.

METHODSWild-type female mice with ICR background (6-8 weeks old) were divided randomly into groups A, B and C (n=12). In groups B and C, the mice were treated with the total protein extract from porcine ovary to induce immunological injury of the ovary, while those in group A received no treatment. MSCs-derived from GFP transgenic mice were transplanted into the mice of group C, and equal volume of PBS was injected intraperitoneally in mice of the other two groups. PCR was used to detect GFP gene in the genomic DNA of the ovaries to assess MSCs homing in the ovary, and the reparative effect of MSCs on ovarian injury was evaluated using HE staining and TUNEL analysis.

RESULTSAfter transplantation, the MSCs could reach the injured ovaries to promote the repair of the ovarian injury, resulting also in reduced apoptosis of the granulosa cells (GCs) in the injured ovaries.

CONCLUSIONMSCs transplantation can promote the recovery of the immunological injury of the ovary in mice, the mechanism of which may involve reduced apoptosis of the GCs.

Animals ; Apoptosis ; Bone Marrow Cells ; Female ; Granulosa Cells ; cytology ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; Mice ; Mice, Inbred ICR ; Ovarian Diseases ; pathology ; surgery ; Ovary ; cytology ; pathology

OBJECTIVETo observe the homing and differentiation of marrow-derived mesenchymal stem cells (MSC) transplanted intravenously in smoke inhalation injured rabbits.

METHODSThirty-two New Zealand big ear rabbits were divided into normal control group (NC), inhalation injury group (II), normal control + MSC treatment group (NM), and MSC treatment group (MT) according to the random number table, with 8 rabbits in each group. Rabbits in NC group were injected with 10 mL phosphate buffered saline (PBS) via ear marginal vein. Rabbits in NM group were injected with 10 mL PBS containing the third generation MSC labeled by BrdU (1 × 10(7) per 10 mL PBS) via ear marginal vein. Severe smoke inhalation injury model was reproduced in the other two groups, among them rabbits in II group were treated as rabbits in NC group, rabbits in MT group treated as rabbits in NM group. On the 7th and 28th day post treatment (PTD), lung tissue and trachea tissue were harvested from four groups for observation on injury with HE staining. Homing of MSC in injured tissue was observed with immunohistochemistry staining. The differentiation of MSC into functional cells was observed with immunohistochemical double staining of combining nuclear marker BrdU with lung (trachea) membrane-specific marker aquaporin-5 (AQP-5), alkaline phosphatase (AKP), CD34, and cytokeratin respectively.

RESULTS(1) MSC homing in lung and trachea tissue was observed in MT group on PTD 7, which was not observed in NM group. (2) AQP-5, AKP, and CD34 positive MSC were observed in lung tissue in MT group on PTD 28, while cytokeratin positive MSC was not observed in trachea tissue. No positively marked MSC was observed in NM group. (3) Injury in lung and trachea was less severe in MT group than in II group; and the proliferation of fibroblasts was less in MT group.

CONCLUSIONSIntravenous injection of MSC to rabbits with smoke inhalation injury can migrate to lung and trachea tissue at obviously inflammatory site, and differentiate into alveolar epithelial cells typeI and II, and pulmonary vascular endothelial cells, which may participate in the process of tissue repair in smoke inhalation injury.

Animals ; Bone Marrow Cells ; cytology ; Cell Differentiation ; Cells, Cultured ; Endothelial Cells ; cytology ; Epithelial Cells ; cytology ; Lung ; cytology ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; cytology ; Pulmonary Alveoli ; cytology ; Rabbits ; Smoke Inhalation Injury ; pathology ; Trachea ; cytology

OBJECTIVETo investigate the biological characteristics of human keloid-derived stem cells (KDSC) in order to further research its role in keloid pathogenesis.

METHODSHuman keloid specimens were harvested to isolate and select KDSC by enzyme digestion and subculturing. Primary and (or) the third generation of KDSC were collected for identification of biological characteristics as follows. (1) After addition of mouse anti-human monoclonal fluorescent antibodies (CD29-PE, CD34-PE, CD44-FITC, CD90-FITC, CD45-PerCP), the expression of cell surface antigen phenotype (CD29, CD34, CD44, CD45, CD90) as well as cell cycle was analyzed by flow cytometry. (2) After addition of mouse anti-human cell keratin (CK19) monoclonal antibody and mouse anti-human vimentin monoclonal antibody, the expression level of CK19 and vimentin was respectively determined with immunocytochemical method. RT-PCR was used to detect the expression of Oct4. The multipotent differentiation capacity of the first generation KDSC was observed with osteogenic, chondrogenic and adipogenic nutrient media.

RESULTSAfter being subcultured, the sizes of cells were similar, and the majority of them were spindle-shaped with disorderly arrangement. The cells highly expressed typical surface markers of mesenchymal stem cells (such as CD29, CD44, and CD90, etc.) with low expression of hematopoietic stem cell surface markers (such as CD34, CD45, etc.). 67.66% of cells were in G0/G1 phase, 26.24% of cells were in G2/M phase, and 6.11% of cells were in S phase. Vimentin was positively expressed in KDSC while CK19 was negatively expressed. The expression of Oct4 was also positive. After being cultured in inducing differentiation media, the cells could differentiate into osteoblasts, chondrocytes, and adipocytes.

CONCLUSIONSStem cells existing in human keloid, which are similar to mesenchymal stem cells, may play an important role in keloid pathogenesis.

Adolescent ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Child ; Coculture Techniques ; Female ; Fibroblasts ; cytology ; Humans ; Keloid ; pathology ; Male ; Mesenchymal Stromal Cells ; cytology ; Skin ; cytology ; Stem Cells ; cytology

OBJECTIVETo review the recent studies about human umbilical cord mesenchymal stem cells (hUCMSCs) and advances in the treatment of spinal cord injury. Data sources Published articles (1983 - 2007) about hUCMSCs and spinal cord injury were selected using Medline. Study selection Articles selected were relevant to development of mesenchymal stem cells (MSCs) for transplantation in spinal cord injury therapy. Of 258 originally identified articles 51 were selected that specifically addressed the stated purpose.

RESULTSRecent work has revealed that hUCMSCs share most of the characteristics with MSCs derived from bone marrow and are more appropriate to transplantation for cell based therapies.

CONCLUSIONSHuman umbilical cord could be regarded as a source of MSCs for experimental and clinical needs. In addition, as a peculiar source of stem cells, hUCMSCs may play an important role in the treatment of spinal cord injury.

Humans ; Mesenchymal Stromal Cells ; cytology ; physiology ; Models, Biological ; Spinal Cord Injuries ; pathology ; therapy ; Stem Cell Transplantation ; Umbilical Cord ; cytology

OBJECTIVESpinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease. It is characterized by selective loss of spinal cord motor neurons leading to muscle atrophy and is the result of mutation or deletion of the survival motor neuron (SMN) gene. Currently, there are no effective therapies for this disease. Stem cell therapy is a new prospect for SMA patients. This study aimed to investigate whether mesenchymal stem cells (MSCs) can be differentiated into neuron-like cells (NLCs) in SMA patients in order to provide a basis for stem cell therapy for SMA.

METHODSSMA was definitively diagnosed using polymerase chain reaction-restriction fragment length polymerphhism (PCR-RFLP). Two children without SMN1 gene deletion were used as controls. MSCs were isolated and purified from SMA patients and controls, and induced into NLCs by bFGF and baicalin. The NLCs were identified by immunofluourescence staining with NSE and NF monoclonal antibodies.

RESULTSSMA patients showed the deletion of SMN1 exon 7. The morphous and proliferative speed of MSCs between SMA patients and controls were similar. After 6-day induction, MSCs of the two groups displayed similar morphology to that of neurons, with long processes forming extensive networks. NSE and NF, the neuronal markers, were detected in the differentiated NLCs of the two groups.

CONCLUSIONSSMN1 deletion appears not to affect the proliferation and differentiation of MSCs. MSCs of SMA patients can be differentiated into NLCs.

Adolescent ; Cell Differentiation ; Cell Proliferation ; Child ; Female ; Humans ; Male ; Mesenchymal Stromal Cells ; cytology ; Muscular Atrophy, Spinal ; pathology ; Neurons ; cytology

OBJECTIVETo establish a method through which murine bone marrow mesenchymal stem cells (MSCs) can be induced into hepatocytes in vitro.

METHODSA conditioned medium of injured hepatocytes (with CCl4 in vivo) was used to culture the isolated MSCs. The differentiated cells were identified by morphological observation, reverse transcription polymerase chain reaction (RT-PCR), immunofluorescence assay (for AFP, Albumin, and CK18) and periodic acid schiff reaction (PAS) for glycogen.

RESULTSThe differentiated cells showed characteristics of hepatocytes. PT-PCR detected AFP mRNA on day 5 and it increased gradually until day 15, and then decreased; CK18 mRNA was detected on day 10; TAT was detected on day 20. Immunofluorescence assay for AFP, albumin and CK18 showed positive staining reactions on day 20. PAS positive glycogen granules appeared in the cytoplasm of the differentiated cells.

CONCLUSIONMSCs of adult mice cultured in a conditioned medium of injured hepatocytes can differentiate into hepatocytes. This method can be used in further studying of the mechanism of transdifferentiation of MSCs into hepatocytes.

Animals ; Bone Marrow Cells ; cytology ; Cell Culture Techniques ; Cell Differentiation ; Cells, Cultured ; Culture Media, Conditioned ; Hepatocytes ; cytology ; Liver ; pathology ; Male ; Mesenchymal Stromal Cells ; cytology ; Mice ; Mice, Inbred ICR

Bone marrow mesenchymal stem cells (MSCs) transplantation could repair injury tissue, but no study confirms whether MSCs can promote the proliferation of endogenous lung stem cells to repair alveolar epithelial cells of mice with chronic obstructive pulmonary disease (COPD). This study was designed to investigate the effect of MSCs on the proliferation of endogenous lung stem cells in COPD mice to confirm the repair mechanism of MSCs. The mice were divided into control group, COPD group, and COPD+MSCs group. The following indexes were detected: HE staining of lung tissue, the mean linear intercept (MLI) and alveolar destructive index (DI), the total cell number in bronchoalveolar lavage fluid (BALF), pulmonary function, alveolar wall apoptosis index (AI) and proliferation index (PI), the number of CD45(-)/CD31(-)/Sca-1(+) cells by flow cytometry (FCM), and the number of bronchoalveolar stem cells (BASCs) in bronchoalveolar duct junction (BADJ) by immunofluorescence. As compared with control group, the number of inflammatory cells in lung tissue was increased, alveolar septa was destroyed and the emphysema-like changes were seen, and the changes of lung function were in line with COPD in COPD group; AI of alveolar wall was significantly increased and PI significantly decreased in COPD group. There was no significant difference in the number of CD45(-)/CD31(-)/Sca-1(+) cells and BASCs between control group and COPD group. As compared with COPD group, the number of inflammatory cells in BALF was decreased, the number of CD45(-)/CD31(-)/Sca-1(+) cells and BASCs was increased, AI of alveolar wall was decreased and PI was increased, and emphysema-like changes were relieved in COPD+MSCs group. These findings suggested that MSCs transplantation can relieve lung injury by promoting proliferation of endogenous lung stem cells in the cigarette smoke-induced COPD mice.
Animals ; Cell Proliferation ; Lung ; pathology ; Mesenchymal Stromal Cells ; cytology ; Mice ; Mice, Inbred C57BL ; Pulmonary Disease, Chronic Obstructive ; pathology ; therapy