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

BACKGROUND: Containing a certain proportion of mesenchymal stem cells, inflammatory dental tissue showed great tissue regeneration potential in recent years. However, whether it is applicable to promote tissue regeneration in vivo remains to be elucidated. Therefore, we evaluated the feasibility of stem cells from inflammatory dental pulp tissues (DPSCs-IPs) to reconstruct periodontal defects in miniature pigs. METHODS: The autologous pig DPSCs-IPs were first cultured, appraised and loaded onto β-tricalcium phosphate (β-TCP). The compounds were then engrafted into an artificially-created periodontal defect. Three months later, the extent of periodontal regeneration was evaluated. Clinical examination, radiological examination and immunohistochemical staining were used to assess periodontal regeneration. RESULTS: The data collectively showed that DPSCs-IPs from miniature pigs expressed moderate to high levels of STRO-1 and CD146 as well as low levels of CD34 and CD45. DPSCs-IPs have osteogentic, adipogenic and chondrogenic differentiation abilities. DPSCs-IPs were engrafted onto β-TCP and regenerated bone to repair periodontal defects by 3 months' post-surgical reconstruction. CONCLUSION: Autologous DPSCs-IPs may be a feasible means of periodontal regeneration in miniature pigs.
Dental Pulp ; Mesenchymal Stromal Cells ; Periodontitis ; Regeneration ; Stem Cells ; Swine ; Swine, Miniature

BACKGROUND: Lonocyte-derived multipotential cells (MOMCs) include progenitors capable of differentiation into multiple cell lineages and thus represent an ideal autologous transplantable cell source for regenerative medicine. In this study, we cultured MOMCs, generated from mononuclear cells of peripheral blood, on the surface of nanocomposite thin films. METHODS: For this purpose, nanocomposite Poly(e-caprolactone) (PCL)-based thin films containing either 2.5 wt% silica nanotubes (SiO2ntbs) or strontium hydroxyapatite nanorods (SrHAnrds), were prepared using the spin-coating method. The induced differentiation capacity of MOMCs, towards bone and endothelium, was estimated using flow cytometry, real-time polymerase chain reaction, scanning electron microscopy and fluorescence microscopy after cells' genetic modification using the Sleeping Beauty Transposon System aiming their observation onto the scaffolds. Moreover, Wharton's Jelly Mesenchymal Stromal Cells were cultivated as a control cell line, while Human Umbilical Vein Endothelial Cells were used to strengthen and accelerate the differentiation procedure in semi-permeable culture systems. Finally, the cytotoxicity of the studied materials was checked with MTT assay. RESULTS: The highest differentiation capacity of MOMCs was observed on PCL/SiO2ntbs 2.5 wt% nanocomposite film, as they progressively lost their native markers and gained endothelial lineage, in both protein and transcriptional level. In addition, the presence of SrHAnrds in the PCL matrix triggered processes related to osteoblast bone formation. CONCLUSION: To conclude, the differentiation of MOMCs was selectively guided by incorporating SiO2ntbs or SrHAnrds into a polymeric matrix, for the first time.
Autografts ; Beauty ; Cell Line ; Cell Lineage ; Durapatite ; Endothelium ; Flow Cytometry ; Human Umbilical Vein Endothelial Cells ; Mesenchymal Stromal Cells ; Methods ; Microscopy, Electron, Scanning ; Microscopy, Fluorescence ; Nanocomposites ; Nanotubes ; Osteoblasts ; Osteogenesis ; Polymers ; Real-Time Polymerase Chain Reaction ; Regenerative Medicine ; Silicon Dioxide ; Strontium ; Wharton Jelly

BACKGROUND: Unlike bone, cartilage, or muscle, tendon-specific markers are not well established. The purpose of the study was to investigate expression pattern and level of 6 well-known tendon-specific markers, in various human musculoskeletal tissues, tenocytes, and mesenchymal stem cells (MSCs). METHODS: Musculoskeletal tissue samples of tendon, bone, cartilage, nerve, muscle, and fat were obtained from patients undergoing orthopedic surgery. Tenocytes, MSCs from bone marrow, adipose tissue, and umbilical cord were isolated from each tissue and cultured. Six tendon-specific markers, scleraxis (Scx), tenomodulin (TNMD), thrombospondin-4 (TSP-4), tenascin-C (TNC), type I collagen (Col I), and type III collagen (Col III) were investigated in tendon tissue, tenocytes, and MSCs. RESULTS: mRNA levels of 6 tendon-specific markers were significantly higher in tendon tissue that in other connective tissues levels of Scx, TNMD, TSP-4, and Col III immediately decreased after plating tenocytes in culture dishes whereas those of TNC and Col I did not. In comparison with tendon tissue, mRNA levels pattern of Scx, TNMD, and TSP-4 in tenocytes were significantly higher than that in MSCs, but lower than in tendon tissue whereas expression pattern of TNC, Col I and III showed different pattern with each other. CONCLUSION: This study demonstrated that 6 commonly used tendon-specific markers were mainly expressed in tendon tissue, but that expression level and pattern of the tendon-specific markers with respect to kinds of tissues, culture duration of tenocytes and sources of MSCs.
Adipose Tissue ; Biomarkers ; Bone Marrow ; Cartilage ; Collagen Type I ; Collagen Type III ; Connective Tissue ; Humans ; Mesenchymal Stromal Cells ; Orthopedics ; RNA, Messenger ; Tenascin ; Tendons ; Umbilical Cord

BACKGROUND: Recent studies have shown that induced pluripotent stem cells (iPSCs) could be differentiated into mesenchymal stem cells (MSCs) with notable advantages over iPSCs per se. In order to promote the application of iPSC-MSCs for osteoregenerative medicine, the present study aimed to assess the ability of murine iPSC-MSCs to differentiate into osteoblast phenotype. METHODS: Osteogenic differentiation medium, blending mouse osteoblast-conditioned medium (CM) with basic medium (BM) at ratio 3:7, 5:5 and 7:3, were administered to iPSC-MSCs, respectively. After 14 days, differentiation was evaluated by lineage-specific morphology, histological stain, quantitative reverse transcription-polymerase chain reaction and immunostaining. RESULTS: The osteogenesis-related genes, alp, runx2, col1 and ocn expressions suggest that culture medium consisting of CM:BM at the ratio of 3:7 enhanced the osteogenic differentiation more than other concentrations that were tested. In addition, the alkaline phosphatase activity and osteogenic marker Runx2 expression demonstrate that the combination of CM and BM significantly enhanced the osteogenic differentiation of iPSC-MSCs. CONCLUSION: In summary, this study has shown that osteoblast-derived CM can dramatically enhance osteogenic differentiation of iPSC-MSCs toward osteoblasts. Results from this work will contribute to optimize the osteogenic induction conditions of iPSC-MSCs and will assist in the potential application of iPSC-MSCs for bone tissue engineering.
Alkaline Phosphatase ; Animals ; Bone and Bones ; Culture Media, Conditioned ; Induced Pluripotent Stem Cells ; Mesenchymal Stromal Cells ; Mice ; Osteoblasts ; Phenotype

BACKGROUND: Liver disease is one of the top causes of death globally. Although liver transplantation is a very effective treatment strategy, the shortage of available donor organs, waiting list mortality, and high costs of surgery remain huge problems. Stem cells are undifferentiated cells that can differentiate into a variety of cell types. Scientists are exploring the possibilities of generating hepatocytes from stem cells as an alternative for the treatment of liver diseases. METHODS: In this review, we summarized the updated researches in the field of stem cell-based therapies for liver diseases as well as the current challenges and future expectations for a successful cell-based liver therapy. RESULTS: Several cell types have been investigated for liver regeneration, such as embryonic stem cells, induced pluripotent stem cells, liver stem cells, mesenchymal stem cells, and hematopoietic stem cells. In vitro and in vivo studies have demonstrated that stem cells are promising cell sources for the liver regeneration. CONCLUSION: Stem cell-based therapy could be a promising therapeutic method for patients with end-stage liver disease, which may alleviate the need for liver transplantation in the future.
Cause of Death ; Embryonic Stem Cells ; Hematopoietic Stem Cells ; Hepatocytes ; Humans ; In Vitro Techniques ; Induced Pluripotent Stem Cells ; Liver Diseases ; Liver Regeneration ; Liver Transplantation ; Liver ; Mesenchymal Stromal Cells ; Methods ; Mortality ; Stem Cells ; Tissue Donors ; Waiting Lists

BACKGROUND: Nowadays, production of nanocomposite scaffolds based on natural biopolymer, bioceramic, and metal ions is a growing field of research due to the potential for bone tissue engineering applications. METHODS: In this study, a nanocomposite scaffold for bone tissue engineering was successfully prepared using collagen (COL), beta-tricalcium phosphate (β-TCP) and strontium oxide (SrO). A composition of β-TCP (4.9 g) was prepared by doping with SrO (0.05 g). Biocompatible porous nanocomposite scaffolds were prepared by freeze-drying in different formulations [COL, COL/β-TCP (1:2 w/w), and COL/β-TCP-Sr (1:2 w/w)] to be used as a provisional matrix or scaffold for bone tissue engineering. The nanoparticles were characterized by X-ray diffraction, Fourier transforms infrared spectroscopy and energy dispersive spectroscopy. Moreover, the prepared scaffolds were characterized by physicochemical properties, such as porosity, swelling ratio, biodegradation, mechanical properties, and biomineralization. RESULTS: All the scaffolds had a microporous structure with high porosity (~ 95–99%) and appropriate pore size (100–200 µm). COL/β-TCP-Sr scaffolds had the compressive modulus (213.44 ± 0.47 kPa) higher than that of COL/β-TCP (33.14 ± 1.77 kPa). In vitro cytocompatibility, cell attachment and alkaline phosphatase (ALP) activity studies performed using rat bone marrow mesenchymal stem cells. Addition of β-TCP-Sr to collagen scaffolds increased ALP activity by 1.33–1.79 and 2.92–4.57 folds after 7 and 14 days of culture, respectively. CONCLUSION: In summary, it was found that the incorporation of Sr into the collagen-β-TCP scaffolds has a great potential for bone tissue engineering applications.
Alkaline Phosphatase ; Animals ; Biopolymers ; Bone and Bones ; Bone Marrow ; Collagen ; Fourier Analysis ; Freeze Drying ; In Vitro Techniques ; Ions ; Mesenchymal Stromal Cells ; Nanocomposites ; Nanoparticles ; Porosity ; Rats ; Spectrum Analysis ; Strontium ; X-Ray Diffraction

BACKGROUND: Three-dimensional (3D) printed bone tissue engineering scaffolds have been widely used in research and clinical applications. β-TCP is a biomaterial commonly used in bone tissue engineering to treat bone defects, and its multifunctionality can be achieved by co-doping different metal ions. Magnesium doping in biomaterials has been shown to alter physicochemical properties of cells and enhance osteogenesis. METHODS: A series of Mg-doped TCP scaffolds were manufactured by using cryogenic 3D printing technology and sintering. The characteristics of the porous scaffolds, such as microstructure, chemical composition, mechanical properties, apparent porosity, etc., were examined. To further study the role of magnesium ions in simultaneously inducing osteogenesis and angiogenesis, human bone marrow mesenchymal stem cells (hBMSCs) and human umblical vein endothelial cells (HUVECs) were cultured in scaffold extracts to investigate cell proliferation, viability, and expression of osteogenic and angiogenic genes. RESULTS: The results showed that Mg-doped TCP scaffolds have the advantages of precise design, interconnected porous structure, and similar compressive strength to natural cancellous bone. hBMSCs and HUVECs exhibit high proliferation rate, cell morphology and viability in a certain amount of Mg²⁺. In addition, this concentration of magnesium can also increase the expression levels of osteogenic and angiogenic biomarkers. CONCLUSION: A certain concentration of magnesium ions plays an important role in new bone regeneration and reconstruction. It can be used as a simple and effective method to enhance the osteogenesis and angiogenesis of bioceramic scaffolds, and support the development of biomaterials and bone tissue engineering scaffolds.
Biocompatible Materials ; Biomarkers ; Bone and Bones ; Bone Marrow ; Bone Regeneration ; Cell Proliferation ; Compressive Strength ; Endothelial Cells ; Humans ; In Vitro Techniques ; Ions ; Magnesium ; Mesenchymal Stromal Cells ; Methods ; Osteogenesis ; Porosity ; Printing, Three-Dimensional ; Veins