scholarly journals Gene Therapy of Multiple Sclerosis Using Interferonβ-Secreting Human Bone Marrow Mesenchymal Stem Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Chung Heon Ryu ◽  
Kwang Ywel Park ◽  
Yun Hou ◽  
Chang Hyun Jeong ◽  
Seong Muk Kim ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Average Score ◽  
Lumbar Spinal Cord ◽  
Therapeutic Effects ◽  
Inflammatory Infiltration

Interferon-beta (IFN-β), a well-established standard treatment for multiple sclerosis (MS), has proved to exhibit clinical efficacy. In this study, we first evaluated the therapeutic effects for MS using human bone marrow-derived mesenchymal stem cells (hBM-MSCs) as delivery vehicles with lesion-targeting capability and IFN-βas therapeutic gene. We also engineered hBM-MSCs to secret IFN-β(MSCs-IFNβ) via adenoviral transduction and confirmed the secretory capacity of MSCs-IFNβby an ELISA assay. MSCs-IFNβ-treated mice showed inhibition of experimental autoimmune encephalomyelitis (EAE) onset, and the maximum and average score for all animals in each group was significantly lower in the MSCs-IFNβ-treated EAE mice when compared with the MSCs-GFP-treated EAE mice. Inflammatory infiltration and demyelination in the lumbar spinal cord also significantly decreased in the MSCs-IFNβ-treated EAE mice compared to PBS- or MSCs-GFP-treated EAE mice. Moreover, MSCs-IFNβtreatment enhanced the immunomodulatory effects, which suppressed proinflammatory cytokines (IFN- and TNF-) and conversely increased anti-inflammatory cytokines (IL-4 and IL-10). Importantly, injected MSCs-IFNβmigrated into inflamed CNS and significantly reduced further injury of blood-brain barrier (BBB) permeability in EAE mice. Thus, our results provide the rationale for designing novel experimental protocols to enhance the therapeutic effects for MS using hBM-MSCs as an effective gene vehicle to deliver the therapeutic cytokines.

scholarly journals Effect of Multiple Intraperitoneal Injections of Human Bone Marrow Mesenchymal Stem Cells on Cuprizone Model of Multiple Sclerosis

2018 ◽  
Vol 22 (5) ◽  
pp. 312-321 ◽  
Author(s):  
Mohsen Marzban ◽  
Kazem Mousavizadeh ◽  
Masoomeh Bakhshayesh ◽  
Nasim Vousooghi ◽  
Gelareh Vakilzadeh ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Marrow Mesenchymal Stem Cells

scholarly journals Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis

Glia ◽  
2009 ◽  
Vol 57 (11) ◽  
pp. 1192-1203 ◽  
Author(s):  
Lianhua Bai ◽  
Donald P. Lennon ◽  
Valerie Eaton ◽  
Kari Maier ◽  
Arnold I. Caplan ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Bone Marrow ◽  
Immune Response ◽  
Mesenchymal Stem Cells ◽  
Animal Models ◽  
Human Bone ◽  
Human Bone Marrow

scholarly journals MicroRNA-27b targets CBFB to inhibit differentiation of human bone marrow mesenchymal stem cells into hypertrophic chondrocytes

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Shuang Lv ◽  
Jinying Xu ◽  
Lin Chen ◽  
Haitao Wu ◽  
Wei Feng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Chondrogenic Differentiation ◽  
Hyaline Cartilage ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Luciferase Reporter ◽  
Therapeutic Effects ◽  
Chondrocyte Differentiation

Abstract Background Human bone marrow-derived mesenchymal stem cells (hBMSCs) have chondrocyte differentiation potential and are considered to be a cell source for cell-transplantation-mediated repair of cartilage defects, including those associated with osteoarthritis (OA). However, chondrocyte hypertrophic differentiation is a major obstacle for the application of hBMSCs in articular cartilage defect treatment. We have previously shown that microRNA-27b (miR-27b) inhibits hypertrophy of chondrocytes from rat knee cartilage. In this study, we investigated the role of miR-27b in chondrocyte hypertrophic differentiation of hBMSCs. Methods Chondrogenic marker and microRNA expression in hBMSC chondrogenic pellets were evaluated using RT-qPCR and immunohistochemistry. The hBMSCs were transfected with miR-27b before inducing differentiation. Gene and protein expression levels were analyzed using RT-qPCR and western blot. Coimmunoprecipitation was used to confirm interaction between CBFB and RUNX2. Luciferase reporter assays were used to demonstrate that CBFB is a miR-27b target. Chondrogenic differentiation was evaluated in hBMSCs treated with shRNA targeting CBFB. Chondrogenic hBMSC pellets overexpressing miR-27b were implanted into cartilage lesions in model rats; therapeutic effects were assessed based on histology and immunohistochemistry. Results The hBMSCs showed typical MSC differentiation potentials. During chondrogenic differentiation, collagen 2 and 10 (COL2 and COL10), SOX9, and RUNX2 expression was upregulated. Expression of miR-140, miR-143, and miR-181a increased over time, whereas miR-27b and miR-221 were downregulated. Cartilage derived from hBMSC and overexpressing miR-27b exhibited higher expression of COL2 and SOX9, but lower expression of COL10, RUNX2, and CBFB than did the control cartilage. CBFB and RUNX2 formed a complex, and CBFB was identified as a novel miR-27b target. CBFB knockdown by shRNA during hBMSC chondrogenic differentiation led to significantly increased COL2 and SOX9 expression and decreased COL10 expression. Finally, miR-27b-overexpressing hBMSC chondrogenic pellets had better hyaline cartilage morphology and reduced expression of hypertrophic markers and tend to increase repair efficacy in vivo. Conclusion MiR-27b plays an important role in preventing hypertrophic chondrogenesis of hBMSCs by targeting CBFB and is essential for maintaining a hyaline cartilage state. This study provides new insights into the mechanism of hBMSC chondrocyte differentiation and will aid in the development of strategies for treating cartilage injury based on hBMSC transplantation.

Candidate kinases for adipogenesis and osteoblastogenesis from human bone marrow mesenchymal stem cells

2021 ◽  
Author(s):  
Xia Yi ◽  
Ping Wu ◽  
Jianyun Liu ◽  
Shan He ◽  
Ying Gong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Transcription Factors ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Cytoplasmic Proteins ◽  
Marrow Mesenchymal Stem Cells

Adipogenesis and osteoblastogenesis (adipo-osteoblastogenesis) are closely related processes involving with the phosphorylation of numerous cytoplasmic proteins and key transcription factors.

Inner ear progenitor cells can be generated in vitro from human bone marrow mesenchymal stem cells

2012 ◽  
Vol 7 (6) ◽  
pp. 757-767 ◽  
Author(s):  
Sarah L Boddy ◽  
Wei Chen ◽  
Ricardo Romero-Guevara ◽  
Lucksy Kottam ◽  
Illaria Bellantuono ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Inner Ear ◽  
Progenitor Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Marrow Mesenchymal Stem Cells
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