Stem Cell Treatment and Osteoarthritis at SIRM
What is Osteoarthritis ?
Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion. A variety of causes include hereditary, developmental, metabolic, and mechanical. OA may initiate processes leading to the loss of cartilage.
When bone surfaces become less well protected by cartilage, bone may be exposed and damaged. As a result of decreased movement secondary to pain, regional muscles may atrophy, and ligaments may become more lax.
Human mesenchymal stem cells inhibit osteoclastogenesis through osteoprotegerin production.
Arthritis Rheum. 2011 Jun;63(6):1658-67
Authors: Oshita K, Yamaoka K, Udagawa N, Fukuyo S, Sonomoto K, Maeshima K, Kurihara R, Nakano K, Saito K, Okada Y, Chiba K, Tanaka Y
Mesenchymal stem cells (MSCs) have been proposed to be a useful tool for treatment of rheumatoid arthritis (RA), not only because of their multipotency but also because of their immunosuppressive effect on lymphocytes, dendritic cells, and other proinflammatory cells.
Since bone destruction caused by activated osteoclasts occurs in RA, we undertook the present study to investigate the effect of MSCs on osteoclast function and differentiation in order to evaluate their potential use in RA therapy.
Autologous bone marrow mesenchymal stem cells implantation for cartilage defects: two cases report.
J Med Assoc Thai. 2011 Mar;94(3):395-400
Authors: Kasemkijwattana C, Hongeng S, Kesprayura S, Rungsinaporn V, Chaipinyo K, Chansiri K
The authors reported the results of autologous bone marrow mesenchymal stem cells (BM-MSCs) implantation in two patients with large traumatic cartilage defects of the knee.
Prospects of stem cell therapy in osteoarthritis.
Regen Med. 2011 May;6(3):351-66
Authors: Roberts S, Genever P, McCaskie A, Bari CD
Osteoarthritis is a common disorder in which there is not only extensive degeneration but also an aberrant attempt at repair in joints.
Stem cell therapy could provide a permanent, biological solution, with all sources of stem cells (embryonic, fetal and adult) showing some degree of potential.
Mesenchymal stromal/stem cells, however, appear to be the leading candidates because of their ability to be sourced from many or all joint tissues. They may also modulate the immune response of individuals, in a manner influenced by local factors.
This biological behavior of stem cells renders the application of regulatory standardizations challenging in comparison to pharmaceutical therapies. However, this would not be an issue if endogenous stem cells were activated to effect repair of an arthritic joint.
Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients.
Int J Rheum Dis. 2011 May;14(2):211-5
Authors: Davatchi F, Abdollahi BS, Mohyeddin M, Shahram F, Nikbin B
Background: Osteoarthritis (OA) is a cartilage degenerative process, involving the immune system, producing local inflammatory reactions, with production of pro-inflammatory cytokines and metalloproteinases. No treatment is still available to improve or reverse the process. Stem cell therapy opened new horizons for treatment of many incurable diseases.
Mesenchymal stem cells (MSCs) due to their multi-lineage potential, immunosuppressive activities, limited immunogenicity and relative ease of growth in culture, have attracted attentions for clinical use. Aim: The aim of this study was to examine whether MSC transplantation could reverse the OA process in the knee joint.
The project was approved by the Tehran University of Medical Sciences Research Committee and Ethical Committee. Patients and Methods: Four patients with knee osteoarthritis were selected for the study. They were aged 55, 57, 65 and 54 years, and had moderate to severe knee OA. After their signed written consent, 30 mL of bone marrow were taken and cultured for MSC growth.
After having enough MSCs in culture (4-5 weeks) and taking in consideration all safety measures, cells were injected in one knee of each patient. Results: The walking time for the pain to appear improved for three patients and remained unchanged for one. The number of stairs they could climb and the pain on visual analog scale improved for all of them. On physical examination, the improvement was mainly for crepitus.
It was minor for the improvement of the range of motion. Conclusion: Results were encouraging, but not excellent. Improvement of the technique may improve the results.
Telomere length, telomerase activity and osteogenic differentiation are maintained in adipose-derived stromal cells from senile osteoporotic SAMP6 mice.
J Tissue Eng Regen Med. 2011 Jun 28;
Authors: Mirsaidi A, Kleinhans KN, Rimann M, Tiaden AN, Stauber M, Rudolph KL, Richards PJ
Adipose tissue provides for a rich and easily accessible source of multipotent stromal cells and thus offers the potential for autologous cell-based therapy for a number of degenerative diseases. Senile osteoporosis is characterized by a reduction in bone quality, which is associated with inadequacies in bone marrow stromal cell (BMSC) differentiation. In the present study, we have characterized adipose-derived stromal cells (ASCs) isolated from aged osteoporotic mice and evaluated their suitability as a source of osteogenic precursor cells.
Significant reductions in both tibia bone quality and telomere length in liver tissue were observed in the senescence-accelerated mouse prone 6 strain (SAMP6), as compared to the control age-matched senescence-accelerated mouse resistant 1 strain (SAMR1), thus confirming osteoporosis and accelerated ageing traits in this model.
ASCs isolated from inguinal fat expressed mesenchymal surface markers and were capable of differentiating along the osteoblast, adipocyte and chondrocyte lineages. Telomere length was not compromised in ASCs from SAMP6 mice but was actually found to be significantly increased as compared to control SAMR1 mice.
Furthermore, ASCs from both strains were comparable in terms of telomerase activity, p21 mRNA expression, SA-β-gal activity and proliferative capacity. The overall osteogenic and adipogenic potential of ASCs was comparable between SAMP6 and SAMR1 strains, as determined by quantitative molecular, biochemical and histological analyses.
In conclusion, adipose tissue may represent a promising autologous cell source for the development of novel bone regenerative therapeutic strategies in the treatment of age-related osteoporosis. Copyright © 2011 John Wiley & Sons, Ltd.
Stem Cell Treatments for Osteoarthritis Streaming NIH research:
Continuous release of bone morphogenetic protein-2 through nano-graphene oxide-based delivery influences the activation of the NF-κB signal transduction pathway.
Related Articles Continuous release of bone morphogenetic protein-2 through nano-graphene oxide-based delivery influences the activation of the NF-κB signal transduction pathway. Int J Nanomedicine. 2017;12:1215-1226 Authors: Zhong C, Feng J, Lin X, Bao Q Abstract Graphene oxide (GO) has been used as a delivery vehicle for small molecule drugs and nucleotides. To further investigate GO as a smart biomaterial for the controlled release of cargo molecules, we hypothesized that GO may be an appropriate delivery vehicle because it releases bone morphogenetic protein 2 (BMP2). GO characterization indicated that the size distribution of the GO flakes ranged from 81.1 nm to 45,749.7 nm, with an approximate thickness of 2 nm. After BMP2 adsorption onto GO, Fourier-transformed infrared spectroscopy (FTIR) and thermal gravimetric analysis were performed. Compared to GO, BMP2-GO did not induce significant changes in the characteristics of the materials. GO continuously released BMP2 for at least 40 days. Bone marrow stem cells (BMSCs) and chondrocytes were treated with BMP2-GO in interleukin-1 media and assessed in terms of cell viability, flow cytometric characterization, and expression of particular mRNA. Compared to GO, BMP2-GO did not induce any significant changes in biocompatibility. We treated osteoarthritic rats with BMP2 and BMP2-GO, which showed significant differences in Osteoarthritis Research Society International (OARSI) scores (P<0.05). Quantitative assessment revealed significant differences compared to that using BMP2 and BMP2-GO (P<0.05). These findings indicate that GO may be potentially used to control the release of carrier materials. The combination of BMP2 and GO slowed the progression of NF-κB-activated degenerative changes in osteoarthritis. Therefore, we infer that our BMP2-GO strategy could alleviate the NF-κB pathway by inducing continuous BMP2 release. PMID: 28243085 [PubMed - indexed for MEDLINE]Read more...
MiR-146b is down-regulated during the chondrogenic differentiation of human bone marrow derived skeletal stem cells and up-regulated in osteoarthritis.
Related Articles MiR-146b is down-regulated during the chondrogenic differentiation of human bone marrow derived skeletal stem cells and up-regulated in osteoarthritis. Sci Rep. 2017 Apr 24;7:46704 Authors: Budd E, de Andrés MC, Sanchez-Elsner T, Oreffo ROC Abstract Articular cartilage injury can result in chondrocyte loss and diminishment of specialised extracellular matrix, which can progress to an osteoarthritic (OA) phenotype. Stem cells have emerged as a favourable approach for articular cartilage regeneration. Identification of miRNAs which influence stem cell fate offers new approaches for application of miRNAs to regenerate articular cartilage. Skeletal stem cells (SSCs) isolated from human bone marrow were cultured as high density micromass' using TGF-β3 to induce chondrogenesis. qPCR and TaqMan qPCR were used to assess chondrogenic gene and miRNA expression. Target prediction algorithms identified potential targets of miR-146b. Transient transfection with miR-146b mimic and western blotting was used to analyse SOX5. Human OA articular chondrocytes were examined for miR-146b expression. Chondrogenic differentiation of human bone marrow derived SSCs resulted in significant down-regulation of miR-146b. Gain of miR-146b function resulted in down-regulation of SOX5. MiR-146b expression was up-regulated in OA chondrocytes. These findings demonstrate the functional role of miR-146b in the chondrogenic differentiation of human bone marrow derived SSCs. MiR-146b may play a role in the pathophysiology of OA. Application of miR-146b combined with stem cell therapy could enhance regeneration of cartilaginous tissue and serve as a potential therapeutic target in the treatment of OA. PMID: 28436462 [PubMed - in process]Read more...