Acute lymphoblastic leukemia (ALL) is a kind of the most common hematopoietic malignancy, its recurrence and drug resistance are closely related to the bone marrow microenvironment. Bone marrow stromal cell (BMSC) is an important part of the bone marrow microenvironment and their interaction with leukemia cells cannot be ignored. BMSC participates in and regulate signaling pathways related to proliferation or apoptosis of ALL cells by secretes cytokines or extracellular matrix proteins, thus affecting the survival of ALL cells. In this review, the research advance of several signaling pathways of the interaction between BMSC and ALL cells was summarized briefly.
Apoptosis ; Bone Marrow ; Bone Marrow Cells ; Humans ; Mesenchymal Stem Cells ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Stromal Cells ; Tumor Microenvironment

OBJECTIVE: To explore the expression of CCN5 in endometriotic tissues and its impact on proliferation, migration and invasion of human endometrial stromal cells (HESCs). METHODS: We collected ovarian endometriosis samples from 20 women receiving laparoscopic surgery and eutopic endometrium samples from 15 women undergoing IVF-ET for comparison of CCN5 expression. Cultured HESCs were transfected with a recombinant adenovirus Ad-CCN5 for CCN5 overexpression or with a CCN5-specific siRNA for knocking down CCN5 expression, and the changes of cell proliferation, migration and invasion were evaluated using CCK-8 assay, wound healing assay and Transwell chamber assay. RT-qPCR and Western blotting were used to examine the expression levels of epithelial-mesenchymal transition (EMT) markers including E-cadherin, N-cadherin, Snail-1 and vimentin in HESCs with CCN5 overexpression or knockdown. RESULTS: CCN5 expression was significantly decreased in ovarian endometriosis tissues as compared with eutopic endometrium samples (P < 0.01). CCN5 overexpression obviously inhibited the proliferation, migration and invasion of HESCs, significantly increased the expression of E-cadherin and decreased the expressions of N-cadherin, Snail-1 and vimentin (P < 0.01). CCN5 knockdown significantly enhanced the proliferation, migration and invasion of HESCs and produced opposite effects on the expressions of E-cadherin, N-cadherin, Snail-1 and vimentin (P < 0.01). CONCLUSION CCN5 can regulate the proliferation, migration and invasion of HESCs and thus plays an important role in EMT of HESCs, suggesting the potential of CCN5 as a therapeutic target for endometriosis.
Cell Movement ; Cell Proliferation ; Endometriosis/metabolism* ; Endometrium/metabolism* ; Epithelial Cells ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Stromal Cells

Therapeutic angiogenesis is an important strategy to rescue ischemic tissues in patients with critical limb ischemia having no other treatment option such as endovascular angioplasty or bypass surgery. Studies indicated so far possibilities of therapeutic angiogenesis using autologous bone marrow mononuclear cells, CD34⁺ cells, peripheral blood mononuclear cells, adipose-derived stem/progenitor cells, and etc. Recent studies indicated that subcutaneous adipose tissue contains stem/progenitor cells that can give rise to several mesenchymal lineage cells. Moreover, these mesenchymal progenitor cells release a variety of angiogenic growth factors including vascular endothelial growth factor, fibroblast growth factor, hepatocyte growth factor and chemokine stromal cell-derived factor-1. Subcutaneous adipose tissues can be harvested by less invasive technique. These biological properties of adipose-derived regenerative cells (ADRCs) implicate that autologous subcutaneous adipose tissue would be a useful cell source for therapeutic angiogenesis in humans. In this review, I would like to discuss biological properties and future perspective of ADRCs-mediated therapeutic angiogenesis.
Angioplasty ; Bone Marrow ; Extremities ; Fibroblast Growth Factors ; Hepatocyte Growth Factor ; Humans ; Intercellular Signaling Peptides and Proteins ; Ischemia ; Mesenchymal Stromal Cells ; Stem Cell Transplantation ; Stem Cells ; Subcutaneous Fat ; Vascular Endothelial Growth Factor A

Mesenchymal stem cells are classified as multipotent stem cells, due to their capability to transdifferentiate into various lineages that develop from mesoderm. Their popular appeal as cell-based therapy was initially based on the idea of their ability to restore tissue because of their differentiation potential in vitro; however, the lack of evidence of their differentiation to target cells in vivo led researchers to focus on their secreted trophic factors and their role as potential powerhouses on regulation of factors under different immunological environments and recover homeostasis. To date there are more than 800 clinical trials on humans related to MSCs as therapy, not to mention that in animals is actively being applied as therapeutic resource, though it has not been officially approved as one. But just as how results from clinical trials are important, so is to reveal the biological mechanisms involved on how these cells exert their healing properties to further enhance the application of MSCs on potential patients. In this review, we describe characteristics of MSCs, evaluate their benefits as tissue regenerative therapy and combination therapy, as well as their immunological properties, activation of MSCs that dictate their secreted factors, interactions with other immune cells, such as T cells and possible mechanisms and pathways involved in these interactions.
Animals ; Dinoprostone ; Homeostasis ; Humans ; Immunomodulation* ; In Vitro Techniques ; Mesenchymal Stromal Cells* ; Mesoderm ; Multipotent Stem Cells ; Regeneration* ; Regenerative Medicine ; T-Lymphocytes ; Toll-Like Receptors

BACKGROUND: The development of a safe and convenient agent that can promote hair growth in patients with androgenetic alopecia remains challenging. OBJECTIVE: This study was designed to investigate the efficacy of a newly developed hair tonic containing a human umbilical cord blood mesenchymal stem cell (hUCB-MSC)-derived conditioned medium in promoting hair growth. METHODS: This double-blind, placebo-controlled clinical study investigated the efficacy of a hair tonic containing an hUCB-MSC-derived conditioned medium in 30 patients with patterned hair loss. Treatment efficacy was determined using phototrichograms to evaluate the density, diameter, and hair growth rate at baseline levels and after 4, 8, and 16 weeks of treatment. RESULTS: The hair density in the group treated with the hair tonic significantly increased from 125.2 to 134.6 hairs/cm2 (p<0.05). In this same group, the thickness of hair also increased from 0.083 to 0.110 mm (p<0.05). Additionally, the hair growth rate increased from 0.285 to 0.338 mm/day (p<0.05). No severe adverse reactions were reported. CONCLUSION: A hair tonic containing an hUCB-MSC-derived conditioned medium could be a new effective alternative to treat patients with androgenetic alopecia.
Alopecia ; Clinical Study ; Culture Media, Conditioned ; Fetal Blood ; Hair Preparations ; Hair ; Humans ; Mesenchymal Stromal Cells ; Treatment Outcome ; Umbilical Cord

OBJECTIVE: Spinal cord injury (SCI) is a very serious health problem, usually caused by a trauma and accompanied by elevated levels of inflammation indicators. Stem cell-based therapy is promising some valuable strategies for its functional recovery. Nestin-positive progenitor and/or stem cells (SC) isolated from pancreatic islets (PI) show mesenchymal stem cell (MSC) characteristics. For this reason, we aimed to analyze the effects of rat pancreatic islet derived stem cell (rPI-SC) delivery on functional recovery, as well as the levels of inflammation factors following SCI.METHODS: rPI-SCs were isolated, cultured and their MSC characteristics were determined through flow cytometry and immunofluorescence analysis. The experimental rat population was divided into three groups : 1) laminectomy & trauma, 2) laminectomy & trauma & phosphate-buffered saline (PBS), and 3) laminectomy+trauma+SCs. Green fluorescent protein (GFP) labelled rPI-SCs were transplanted into the injured rat spinal cord. Their motilities were evaluated with Basso, Beattie and Bresnahan (BBB) Score. After 4-weeks, spinal cord sections were analyzed for GFP labeled SCs and stained for vimentin, S100β, brain derived neurotrophic factor (BDNF), 2’,3’-cyclic-nucleotide 3'-phosphodiesterase (CNPase), vascular endothelial growth factor (VEGF) and proinflammatory (interleukin [IL]-6, transforming growth factor [TGF]-β, macrophage inflammatory protein [MIP]-2, myeloperoxidase [MPO]) and anti-inflammatory (IL-1 receptor antagonis) factors.RESULTS: rPI-SCs were revealed to display MSC characteristics and express neural and glial cell markers including BDNF, glial fibrillary acidic protein (GFAP), fibronectin, microtubule associated protein-2a,b (MAP2a,b), β3-tubulin and nestin as well as antiinflammatory prostaglandin E2 receptor, EP3. The BBB scores showed significant motor recovery in group 3. GFP-labelled cells were localized on the injury site. In addition, decreased proinflammatory factor levels and increased intensity of anti-inflammatory factors were determined.CONCLUSION: Transplantation of PI-SCs might be an effective strategy to improve functional recovery following spinal cord trauma.
Animals ; Brain-Derived Neurotrophic Factor ; Dinoprostone ; Fibronectins ; Flow Cytometry ; Fluorescent Antibody Technique ; Glial Fibrillary Acidic Protein ; Inflammation ; Islets of Langerhans ; Laminectomy ; Macrophages ; Mesenchymal Stromal Cells ; Microtubules ; Nestin ; Neuroglia ; Peroxidase ; Rats ; Regeneration ; Spinal Cord Injuries ; Spinal Cord ; Stem Cell Transplantation ; Stem Cells ; Transforming Growth Factors ; Vascular Endothelial Growth Factor A ; Vimentin ; Wounds and Injuries

BACKGROUND: Secretome refers to the total set of molecules secreted or surface-shed by stem cells. The limitations of stem cell research have led numerous investigators to turn their attention to the use of secretome instead of stem cells. In this study, we intended to reinforce antifibrotic properties of the secretome released from adipose-derived stem cells (ASCs) transfected with miR-214. METHODS: We generated miR-214-transfected ASCs, and extracted the secretome (miR214-secretome) from conditioned media of the transfected ASCs through a series of ultrafiltrations. Subsequently, we intravenously injected the miR-214-secretome into mice with liver fibrosis, and determined the effects of miR-214-secretome on liver fibrosis. RESULTS: Compared with that by naïve secretome, liver fibrosis was ameliorated by intravenous infusion of miR-214-secretome into mice with liver fibrosis, which was demonstrated by significantly lower expression of fibrosis-related markers (alpha-smooth muscle actin, transforming growth factor-β, and metalloproteinases-2) in the livers as well as lower fibrotic scores in the special stained livers compared with naïve secretome. The infusion of miR-214-secretome also led to lesser local and systemic inflammation, higher expression of an antioxidant enzyme (superoxide dismutase), and higher liver proliferative and synthetic function. CONCLUSION: MicroRNA-214 transfection stimulates ASCs to release the secretome with higher antifibrotic and anti-inflammatory properties. miR-214-secretome is thus expected to be one of the prominent ways of overcoming liver fibrosis, if further studies consistently validate its safety and efficiency.
Actins ; Animals ; Culture Media, Conditioned ; Humans ; Inflammation ; Infusions, Intravenous ; Liver ; Liver Cirrhosis ; Mesenchymal Stromal Cells ; Mice ; MicroRNAs ; Research Personnel ; Stem Cell Research ; Stem Cells ; Transfection

PURPOSE: Increased bone regeneration has been achieved through the use of stem cells in combination with graft material. However, the survival of transplanted stem cells remains a major concern. The purpose of this study was to evaluate the viability of transplanted mesenchymal stem cells (MSCs) at an early time point (24 hours) based on the type and form of the scaffold used, including type I collagen membrane and synthetic bone. METHODS: The stem cells were obtained from the periosteum of the otherwise healthy dental patients. Four symmetrical circular defects measuring 6 mm in diameter were made in New Zealand white rabbits using a trephine drill. The defects were grafted with 1) synthetic bone (β-tricalcium phosphate/hydroxyapatite [β-TCP/HA]) and 1×105 MSCs, 2) collagen membrane and 1×105 MSCs, 3) β-TCP/HA+collagen membrane and 1×105 MSCs, or 4) β-TCP/HA, a chipped collagen membrane and 1×105 MSCs. Cellular viability and the cell migration rate were analyzed. RESULTS: Cells were easily separated from the collagen membrane, but not from synthetic bone. The number of stem cells attached to synthetic bone in groups 1, 3, and 4 seemed to be similar. Cellular viability in group 2 was significantly higher than in the other groups (P<0.05). The cell migration rate was highest in group 2, but this difference was not statistically significant (P>0.05). CONCLUSIONS: This study showed that stem cells can be applied when a membrane is used as a scaffold under no or minimal pressure. When space maintenance is needed, stem cells can be loaded onto synthetic bone with a chipped membrane to enhance the survival rate.
Bone Regeneration ; Bone Transplantation ; Cell Movement ; Cell Survival ; Collagen ; Collagen Type I ; Humans ; Membranes ; Mesenchymal Stromal Cells ; Periosteum ; Rabbits ; Space Maintenance, Orthodontic ; Stem Cells ; Survival Rate ; Tissue Scaffolds ; Transplants

OBJECTIVE: To explore the effect of damage of bone marrow stroma cells induced by chemotherapeutic drug on the function of normal hematopoitic cells. METHODS: Senescence cells were detected by flow cytometry after SA-β-gal staining; real-time PCR was used to detect the expression of a serial molecules in bone marrow stromal cell line OP9 cells; the expression of γ-H2AX was determined by flow cytometry after histone γ-H2AX staining; the colony forming ability of hematopoietic cells was tested by colony formation assay. RESULTS: The percentage of senescence cells in OP9 cells after DNR treatment was 2.24 times as much as that in untreated OP9 cells (P<0.05). Compared with normal OP9 cells, the expression levels of IL-6 and TNF-alpha in DNR-treated OP9 cells increased by 2.73 times (P<0.01) and 0.56 times (P<0.01), and the expression levels of N-cadherin, alpha smooth muscle actin (alpha-SMA), angiopoietin1 (Angpt1) and osteopontin (OPN) decreased by 69.54%（P<0.01），63.90%（P<0.01），87.41%（P<0.01）and 42.78%（P<0.01）respectively. After the co-culture with DNR-treated OP9 cells, the colony formation of normal hematopoietic cells decreased by 47.10% than that co-cultured with untreated OP9 cells (P< 0.05), meanwhile, the percentage of γ-H2AX+ cells in normal hematopoietic cells increased by 2.19 times (P<0.05). CONCLUSION After treatment with DNR, the senescence cell number of OP9 cells sgnificantly increases; the expression of TNF-α and IL-6 is up-regulated, while the expression of α-SMA, Angpt-1 and OPN is down-regulated as compared with normal OP9 cells. In addition, after co-culture of DNR-treated OP9 cells with normal hematopoietic cells, the colony formation ability of hematopoietic cells decreases and the genome instability of hematopoietic cells increases as compared with normal hematopoietic cells.
Animals ; Bone Marrow ; Bone Marrow Cells ; Cells, Cultured ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Mesenchymal Stem Cells ; Mice ; Stromal Cells

BACKGROUND: Mesenchymal stem cells (MSCs) can be used for a wide range of therapeutic applications because of not only their differentiation potential but also their ability to secrete bioactive factors. Recently, several studies have suggested the use of human embryonic stem cell-derived MSCs (hE-MSCs) as an alternative for regenerative cellular therapy due to mass production of MSCs from a single donor. METHODS: We generated hE-MSCs from embryonic stem cell lines, SNUhES3, and analyzed immune properties of these cells. Also, we evaluated the in-vivo therapeutic potential of hE-MSCs in immune-mediated inflammatory skin disease. RESULTS: The cell showed the suppression of immunity associated with allogenic peripheral blood mononuclear cells in mixed lymphocyte response assay. We also detected that cytokines and growth factor related to the immune response were secreted from these cells. To assessed the in-vivo therapeutic potential of hE-MSCs in immune-mediated inflammatory skin disease, we used imiquimod (IMQ)-induced skin psoriasis mouse model. The score of clinical skin was significantly reduced in the hE-MSCs treated group compared with control IMQ group. In histological analysis, the IMQ-induced epidermal thickness was significantly decreased by hE-MSCs treatment. It was correlated with splenomegaly induced by IMQ which was also improved in the hE-MSCs. Moreover, IMQ-induced inflammatory cytokines; Th1 cytokines (TNF-α, IFN-α, IFN-γ,and IL-27) and Th17 cytokines (IL-17A and IL-23), in the serum and skin showed marked inhibition by hEMSCs. CONCLUSION: These results suggested that hE-MSCs have a potency of immune modulation in psoriasis, which might be the key factor for the improved psoriasis.
Animals ; Cytokines ; Embryonic Stem Cells ; Humans ; Lymphocytes ; Mesenchymal Stromal Cells ; Mice ; Psoriasis ; Skin Diseases ; Skin ; Splenomegaly ; Tissue Donors