Evaluation of Efficacy and Safety of Stem Cells as a Therapeutics, Especially Focusing on Bone Marrow Derived Stromal Cells

2007 ◽  
pp. 137-140
Author(s):  
Ho Sun Jung ◽  
Min Sung Park ◽  
Seung Hwan Han ◽  
Jin Woo Lee
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stromal Cells ◽  
Efficacy And Safety

scholarly journals Biological and microbiological interactions of Ti-35Nb-7Zr alloy and its basic elements on bone marrow stromal cells: good prospects for bone tissue engineering

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Daphne de Camargo Reis Mello ◽  
Lais Morandini Rodrigues ◽  
Fabia Zampieri D’Antola Mello ◽  
Thais Fernanda Gonçalves ◽  
Bento Ferreira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Differentiation ◽  
Stromal Cells ◽  
Biofilm Formation ◽  
Bone Marrow Stromal Cells ◽  
Pure Titanium ◽  
Marrow Stromal Cells ◽  
The Other ◽  
Cell Based Therapy

Abstract Background An effective biomaterial for bone replacement should have properties to avoid bacterial contamination and promote bone formation while inducing rapid cell differentiation simultaneously. Bone marrow stem cells are currently being investigated because of their known potential for differentiation in osteoblast lineage. This makes these cells a good option for stem cell-based therapy. We have aimed to analyze, in vitro, the potential of pure titanium (Ti), Ti-35Nb-7Zr alloy (A), niobium (Nb), and zirconia (Zr) to avoid the microorganisms S. aureus (S.a) and P. aeruginosa (P.a). Furthermore, our objective was to evaluate if the basic elements of Ti-35Nb-7Zr alloy have any influence on bone marrow stromal cells, the source of stem cells, and observe if these metals have properties to induce cell differentiation into osteoblasts. Methods Bone marrow stromal cells (BMSC) were obtained from mice femurs and cultured in osteogenic media without dexamethasone as an external source of cell differentiation. The samples were divided into Ti-35Nb-7Zr alloy (A), pure titanium (Ti), Nb (niobium), and Zr (zirconia) and were characterized by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). After predetermined periods, cell interaction, cytotoxicity, proliferation, and cell differentiation tests were performed. For monotypic biofilm formation, standardized suspensions (106 cells/ml) with the microorganisms S. aureus (S.a) and P. aeruginosa (P.a) were cultured for 24 h on the samples and submitted to an MTT test. Results All samples presented cell proliferation, growth, and spreading. All groups presented cell viability above 70%, but the alloy (A) showed better results, with statistical differences from Nb and Zr samples. Zr expressed higher ALP activity and was statistically different from the other groups (p < 0.05). In contrast, no statistical difference was observed between the samples as regards mineralization nodules. Lower biofilm formation of S.a and P.a. was observed on the Nb samples, with statistical differences from the other samples. Conclusion Our results suggest that the basic elements present in the alloy have osteoinductive characteristics, and Zr has a good influence on bone marrow stromal cell differentiation. We also believe that Nb has the best potential for reducing the formation of microbial biofilms.

The role of children's bone marrow mesenchymal stromal cells in the ex vivo expansion of autologous and allogeneic hematopoietic stem cells

2015 ◽  
Vol 39 (10) ◽  
pp. 1099-1110 ◽  
Author(s):  
Iordanis Pelagiadis ◽  
Eftichia Stiakaki ◽  
Christianna Choulaki ◽  
Maria Kalmanti ◽  
Helen Dimitriou
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Hematopoietic Stem

scholarly journals Major Histocompatibility Complex Restriction Between Hematopoietic Stem Cells and Stromal Cells In Vivo

Blood ◽  
1997 ◽  
Vol 89 (1) ◽  
pp. 49-54 ◽  
Author(s):  
Futoshi Hashimoto ◽  
Kikuya Sugiura ◽  
Kyoichi Inoue ◽  
Susumu Ikehara
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Major Histocompatibility Complex ◽  
Hematopoietic Stem Cells ◽  
Stromal Cells ◽  
Graft Failure ◽  
Major Histocompatibility ◽  
Hematopoietic Stem ◽  
Histocompatibility Complex ◽  
Colony Forming Units

Graft failure is a mortal complication in allogeneic bone marrow transplantation (BMT); T cells and natural killer cells are responsible for graft rejection. However, we have recently demonstrated that the recruitment of donor-derived stromal cells prevents graft failure in allogeneic BMT. This finding prompted us to examine whether a major histocompatibility complex (MHC) restriction exists between hematopoietic stem cells (HSCs) and stromal cells. We transplanted bone marrow cells (BMCs) and bones obtained from various mouse strains and analyzed the cells that accumulated in the engrafted bones. Statistically significant cell accumulation was found in the engrafted bone, which had the same H-2 phenotype as that of the BMCs, whereas only few cells were detected in the engrafted bones of the third-party H-2 phenotypes during the 4 to 6 weeks after BMT. Moreover, the BMCs obtained from the MHC-compatible bone showed significant numbers of both colony-forming units in culture (CFU-C) and spleen colony-forming units (CFU-S). These findings strongly suggest that an MHC restriction exists between HSCs and stromal cells.

scholarly journals Effect of nutritional supplement on bone marrow-derived mesenchymal stem cells from aplastic anaemia

2018 ◽  
Vol 119 (7) ◽  
pp. 748-758
Author(s):  
Shihua Luo ◽  
Yinghai Chen ◽  
Lifen Zhao ◽  
Xia Qi ◽  
Xiaoyan Miao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Aplastic Anaemia ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Nutritional Supplement ◽  
High Dose ◽  
Intragastric Administration ◽  
Dependent Manner ◽  
Mineral Density

AbstractAplastic anaemia (AA) is characterised by pancytopenia resulting from a marked reduction in haemopoietic stem cells (HSC). The regulation of haemopoiesis depends on the interaction between HSC and various cells of the bone marrow (BM) microenvironment, including BM-derived mesenchymal stromal cells (BMSC). The purpose of this study was to analyse the biological effect of nutritional supplement (NS), a dietary supplement consisting of thirty-six compounds: amino acids, nucleotides, vitamins and micronutrients on the BMSC of AA rats. The AA rat model was established by irradiating X-ray (2·5 Gy) and intraperitoneal injections of cyclophosphamide (35 mg/kg; Sigma) and chloramphenicol (35 mg/kg; Sigma). Then AA rats were fed with NS in a dose-dependent manner (2266·95, 1511·3, 1057·91 mg/kg d) by intragastric administration. The effect of NS on the BMSC of AA rats was analysed. As compared with AA rats, NS treatment significantly improved these peripheral blood parameters and stimulated the proliferation of total femoral nucleated cells. NS treatment affected proliferative behaviour of BMSC and suppressed BMSC differentiation to adipocytes. Furthermore, NS treatment of AA rats accelerated osteogenic differentiation of BMSC and enhanced bone mineral density. Co-incubation of HSC with mesenchymal stromal cells and serum from AA rats subjected to high-dose NS markedly improved the yield of CD34+cells. Protein microarray analysis revealed that there were eleven differentially expressed proteins in the NS group compared with the AA rat group. The identified specific NS might be implicated in rehabilitation of BMSC in AA rats, suggesting their potential of nutritional support in AA treatment.

scholarly journals The quiescent fraction of chronic myeloid leukemic stem cells depends on BMPR1B, Stat3 and BMP4-niche signals to persist in patients in remission

Haematologica ◽  
2020 ◽  
Vol 106 (1) ◽  
pp. 111-122 ◽  
Author(s):  
Sandrine Jeanpierre ◽  
Kawtar Arizkane ◽  
Supat Thongjuea ◽  
Elodie Grockowiak ◽  
Kevin Geistlich ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Tyrosine Kinase ◽  
Stromal Cells ◽  
Kinase Inhibitor ◽  
Bmp Signaling ◽  
Myelogenous Leukemia ◽  
Leukemic Stem Cells ◽  
Hematopoietic Stem

Chronic myelogenous leukemia arises from the transformation of hematopoietic stem cells by the BCR-ABL oncogene. Though transformed cells are predominantly BCR-ABL-dependent and sensitive to tyrosine kinase inhibitor treatment, some BMPR1B+ leukemic stem cells are treatment-insensitive and rely, among others, on the bone morphogenetic protein (BMP) pathway for their survival via a BMP4 autocrine loop. Here, we further studied the involvement of BMP signaling in favoring residual leukemic stem cell persistence in the bone marrow of patients having achieved remission under treatment. We demonstrate by single-cell RNA-Seq analysis that a sub-fraction of surviving BMPR1B+ leukemic stem cells are co-enriched in BMP signaling, quiescence and stem cell signatures, without modulation of the canonical BMP target genes, but enrichment in actors of the Jak2/Stat3 signaling pathway. Indeed, based on a new model of persisting CD34+CD38- leukemic stem cells, we show that BMPR1B+ cells display co-activated Smad1/5/8 and Stat3 pathways. Interestingly, we reveal that only the BMPR1B+ cells adhering to stromal cells display a quiescent status. Surprisingly, this quiescence is induced by treatment, while non-adherent BMPR1B+ cells treated with tyrosine kinase inhibitors continued to proliferate. The subsequent targeting of BMPR1B and Jak2 pathways decreased quiescent leukemic stem cells by promoting their cell cycle re-entry and differentiation. Moreover, while Jak2-inhibitors alone increased BMP4 production by mesenchymal cells, the addition of the newly described BMPR1B inhibitor (E6201) impaired BMP4-mediated production by stromal cells. Altogether, our data demonstrate that targeting both BMPR1B and Jak2/Stat3 efficiently impacts persisting and dormant leukemic stem cells hidden in their bone marrow microenvironment.

scholarly journals Deciphering Master Gene Regulators and Associated Networks of Human Mesenchymal Stromal Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 557
Author(s):  
Elena Sánchez-Luis ◽  
Andrea Joaquín-García ◽  
Francisco J. Campos-Laborie ◽  
Fermín Sánchez-Guijo ◽  
Javier De las Rivas
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Transcription Factors ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Structure ◽  
Regulatory Gene ◽  
Human Mscs ◽  
Protein Activity ◽  
Hematopoietic Stem

Mesenchymal Stromal Cells (MSC) are multipotent cells characterized by self-renewal, multilineage differentiation, and immunomodulatory properties. To obtain a gene regulatory profile of human MSCs, we generated a compendium of more than two hundred cell samples with genome-wide expression data, including a homogeneous set of 93 samples of five related primary cell types: bone marrow mesenchymal stem cells (BM-MSC), hematopoietic stem cells (HSC), lymphocytes (LYM), fibroblasts (FIB), and osteoblasts (OSTB). All these samples were integrated to generate a regulatory gene network using the algorithm ARACNe (Algorithm for the Reconstruction of Accurate Cellular Networks; based on mutual information), that finds regulons (groups of target genes regulated by transcription factors) and regulators (i.e., transcription factors, TFs). Furtherly, the algorithm VIPER (Algorithm for Virtual Inference of Protein-activity by Enriched Regulon analysis) was used to inference protein activity and to identify the most significant TF regulators, which control the expression profile of the studied cells. Applying these algorithms, a footprint of candidate master regulators of BM-MSCs was defined, including the genes EPAS1, NFE2L1, SNAI2, STAB2, TEAD1, and TULP3, that presented consistent upregulation and hypomethylation in BM-MSCs. These TFs regulate the activation of the genes in the bone marrow MSC lineage and are involved in development, morphogenesis, cell differentiation, regulation of cell adhesion, and cell structure.

scholarly journals Major Histocompatibility Complex Restriction Between Hematopoietic Stem Cells and Stromal Cells In Vivo

Blood ◽  
1997 ◽  
Vol 89 (1) ◽  
pp. 49-54 ◽  
Author(s):  
Futoshi Hashimoto ◽  
Kikuya Sugiura ◽  
Kyoichi Inoue ◽  
Susumu Ikehara
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Major Histocompatibility Complex ◽  
Hematopoietic Stem Cells ◽  
Stromal Cells ◽  
Graft Failure ◽  
Major Histocompatibility ◽  
Hematopoietic Stem ◽  
Histocompatibility Complex ◽  
Colony Forming Units

Abstract Graft failure is a mortal complication in allogeneic bone marrow transplantation (BMT); T cells and natural killer cells are responsible for graft rejection. However, we have recently demonstrated that the recruitment of donor-derived stromal cells prevents graft failure in allogeneic BMT. This finding prompted us to examine whether a major histocompatibility complex (MHC) restriction exists between hematopoietic stem cells (HSCs) and stromal cells. We transplanted bone marrow cells (BMCs) and bones obtained from various mouse strains and analyzed the cells that accumulated in the engrafted bones. Statistically significant cell accumulation was found in the engrafted bone, which had the same H-2 phenotype as that of the BMCs, whereas only few cells were detected in the engrafted bones of the third-party H-2 phenotypes during the 4 to 6 weeks after BMT. Moreover, the BMCs obtained from the MHC-compatible bone showed significant numbers of both colony-forming units in culture (CFU-C) and spleen colony-forming units (CFU-S). These findings strongly suggest that an MHC restriction exists between HSCs and stromal cells.

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