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

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

STUDY DESIGN: Experimental study. PURPOSE: To determine whether epidural fat (EF) tissue contains mesenchymal stem cells (MSC). OVERVIEW OF LITERATURE: Spine surgeons are unaware of the contents of EF tissue and the reason for its presence between the ligamentum flavum and the dura mater; therefore, EF tissues are routinely eliminated during surgical procedures. However, EF removal causes certain postoperative problems, such as post-laminectomy syndrome. We hypothesized that the EF tissue may play a significant supportive role for the neural structures and other nearby conditions. METHODS: EF tissues were obtained from consenting patients (n=3) during posterior decompression surgery of the lumbar spine. The primary cells were isolated and cultured as per previously described methods with some modifications, and the cell morphology and cumulation were examined. Thereafter, reverse transcription–polymerase chain reaction (RT-PCR), a fluorescence-activated cell sorting (FACS) analysis, and differentiation potency for differentiation into osteoblasts, chondroblasts, and adipocytes were investigated to identify whether the cells derived from EF are MSC. RESULTS: The cells from the EF tissue had a fibroblast or neuron-like morphology that persisted until the senescence at p18. MSC-specific genes, such as OCT4, SOX2, KLF4, MYC, and GAPDH were expressed in the RT-PCR study, while MSC-specific surface markers such as CD105, CD90, and CD73 were exhibited in the FACS analysis. The differentiation properties of EF-MSC for differentiation into the three types of cells (osteoblast, chondroblast, and adipocyte) were also confirmed. CONCLUSIONS: Based on the cell culture, FACS analysis, RT-PCR analysis, and differentiation potent outcomes, all the features of the cells corresponded to MSC. This is the first study to identify EF-MSC derived from the EF tissue.
Adipocytes ; Aging ; Cell Culture Techniques ; Chondrocytes ; Decompression ; Dura Mater ; Fibroblasts ; Flow Cytometry ; Humans ; Ligamentum Flavum ; Mesenchymal Stromal Cells ; Osteoblasts ; Spine ; Surgeons

Drug resistance in cancer, especially in leukemia, creates a dilemma in treatment planning. Consequently, studies related to the mechanisms underlying drug resistance, the molecular pathways involved in this phenomenon, and alternate therapies have attracted the attention of researchers. Among a variety of therapeutic modalities, mesenchymal stem cells (MSCs) are of special interest due to their potential clinical use. Therapies involving MSCs are showing increasing promise in cancer treatment and anticancer drug screening applications; however, results have been inconclusive, possibly due to the heterogeneity of MSC populations. Most recently, the effect of MSCs on different types of cancer, such as hematologic malignancies, their mechanisms, sources of MSCs, and its advantages and disadvantages have been discussed. There are many proposed mechanisms describing the effects of MSCs in hematologic malignancies; however, the most commonly-accepted mechanism is that MSCs induce tumor cell cycle arrest. This review explains the anti-tumorigenic effects of MSCs through the suppression of tumor cell proliferation in hematological malignancies, especially in acute myeloid leukemia.
Cell Cycle Checkpoints ; Cell Proliferation ; Drug Evaluation, Preclinical ; Drug Resistance ; Hematologic Neoplasms ; Leukemia ; Leukemia, Myeloid, Acute ; Mesenchymal Stromal Cells ; Population Characteristics

With the progress of regenerative medicine, mesenchymal stem cells (MSCs) have received attention as a way to restore ovarian function. It has been reported that MSCs derived from bone marrow, adipose, umbilical cord blood, menstrual blood, and amniotic fluid improved ovarian function. In light of previous studies and advances in this field, there are increased expectations regarding the utilization of MSCs to restore ovarian function. This review summarizes recent research into potential applications of MSCs in women with infertility or primary ovarian insufficiency, including cases where these conditions are induced by anticancer therapy.
Amniotic Fluid ; Bone Marrow ; Female ; Fetal Blood ; Humans ; Infertility ; Mesenchymal Stromal Cells ; Primary Ovarian Insufficiency ; Regenerative Medicine

BACKGROUND: Fluoranthene (FR) is a common environmental pollutant that exists in a complex mixture with other polycyclic aromatic hydrocarbons (PAHs). We identified biomarkers for monitoring FR exposure and investigated the rescue effect of FR-induced cellular toxicity via aryl hydrocarbon receptor (AHR) antagonist activity in bone marrow derived mesenchymal stem cells (BM-MSCs).METHODS: Morphological changes, viability, and rescue effects of an AHR antagonist (CH223191) were examined in BM-MSCs after exposure to FR. Cytotoxic effects were assayed using the tetrazolium-based colorimetric assay. Apoptosis was measured by annexin V and propidium iodide dye-based flowcytometry assay, mitochondrial membrane potential assay, and nuclear DNA fragmentation assay. Molecular signaling pathways of apoptosis and autophagy were investigated using immunoblotting. Proteomics were performed in order to reveal the spectra of cellular damage and identify biomarkers for FR exposure.RESULTS: Exposing BM-MSCs to FR (IC₅₀=50 µM) induced cell death and morphological changes, while the AHR antagonist showed rescue effects. Autophagy was activated and mitochondrial membrane potential was decreased. Proteomic analysis identified 48 deregulated proteins (26 upregulated and 22 downregulated). Among them, annexin A6, pyruvate kinase, UDP-glucose dehydrogenase, and phospholipase A2 could be potential biomarkers for FR exposure.CONCLUSION: The exposure of BM-MSCs to FR induced remarkable alterations in cellular biology and the proteome, allowing for identification of novel biomarkers for FR exposure. Furthermore, AHR antagonists might be able to prevent cellular damage due to FR exposure.
Annexin A5 ; Annexin A6 ; Apoptosis ; Autophagy ; Biomarkers ; Bone Marrow ; Cell Death ; DNA Fragmentation ; Immunoblotting ; Membrane Potential, Mitochondrial ; Mesenchymal Stromal Cells ; Oxidoreductases ; Phospholipases A2 ; Polycyclic Hydrocarbons, Aromatic ; Propidium ; Proteome ; Proteomics ; Pyruvate Kinase ; Receptors, Aryl Hydrocarbon

Obesity, diabetes, and cardiovascular diseases are increasing rapidly worldwide and it is therefore important to know the effect of exercise and medications for diabetes and obesity on adult stem cells. Adult stem cells play a major role in remodeling and tissue regeneration. In this review we will focus mainly on two adult stem/progenitor cells such as endothelial progenitor cells and mesenchymal stromal cells in relation to aerobic exercise and diabetes medications, both of which can alter the course of regeneration and tissue remodelling. These two adult precursor and stem cells are easily obtained from peripheral blood or adipose tissue depots, as the case may be and are precursors to endothelium and mesenchymal tissue (fat, bone, muscle, and cartilage). They both are key players in maintenance of cardiovascular and metabolic homeostasis and can act also as useful biomarkers.
Adipose Tissue ; Adult Stem Cells ; Adult ; Biomarkers ; Cardiovascular Diseases ; Diabetes Mellitus, Type 2 ; Endothelial Progenitor Cells ; Endothelium ; Exercise ; Hematopoietic Stem Cells ; Homeostasis ; Humans ; Mesenchymal Stromal Cells ; Obesity ; Regeneration ; Stem Cells

BACKGROUND AND OBJECTIVES: Most studies in cardiac regeneration have explored bone marrow mesenchymal stem cells (BM-MSC) with variable therapeutic effects. Amniotic fluid MSC (AF-MSC) having extended self-renewal and multi-potent properties may be superior to bone marrow MSC (BM-MSC). However, a comparison of their cardiomyogenic potency has not been studied yet.METHODS: The 5-azacytidine (5-aza) treated AF-MSC and BM-MSC were evaluated for the expression of GATA-4, Nkx2.5 and ISL-1 transcripts and proteins by quantitative RT-PCR and Western blotting, respectively as well as for the expression of cardiomyogenic differentiation markers cardiac troponin-T (cTNT), beta myosin heavy chain (βMHC) and alpha sarcomeric actinin (ASA) by immunocytochemistry.RESULTS: The AF-MSC as compared to BM-MSC had significantly higher expression of GATA-4 (183.06±29.85 vs. 9.80±0.05; p<0.01), Nkx2.5 (8.3±1.4 vs. 1.82±0.32; p<0.05), and ISL-1 (39.59±4.05 vs. 4.36±0.39; p<0.01) genes as well as GATA-4 (2.01±0.5 vs. 0.6±0.1; p<0.05), NKx2.5 (1.9±0.14 vs. 0.8±0.2; p<0.01) and ISL-1 (1.7±0.3 vs. 0.9±0.1; p<0.05) proteins. The AF-MSC also had significantly elevated expression of cTNT (5.0×10⁴±0.6×10⁴ vs. 3.5 ×10⁴±0.8×10⁴; p<0.01), β-MHC (15.7×10⁴±0.9×10⁴ vs. 8.2×10⁴±0.6×10⁴; p<0.01) and ASA (18.6×10⁴±4.9×10⁴ vs. 13.1×10⁴±3.0×10⁴; p<0.05) than BM-MSC.CONCLUSIONS: Our data suggest that AF-MSC have greater cardiomyogenic potency than BM-MSC, and thus may be a better source of MSC for therapeutic applications in cardiac regenerative medicine.
Actinin ; Amniotic Fluid ; Antigens, Differentiation ; Azacitidine ; Blotting, Western ; Bone Marrow ; Female ; Humans ; Immunohistochemistry ; Mesenchymal Stromal Cells ; Regeneration ; Regenerative Medicine ; Therapeutic Uses ; Troponin T ; Ventricular Myosins