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:
Cell-Based Meniscus Repair and Regeneration: At the Brink of Clinical Translation?: A Systematic Review of Preclinical Studies.
Related Articles Cell-Based Meniscus Repair and Regeneration: At the Brink of Clinical Translation?: A Systematic Review of Preclinical Studies. Orthop J Sports Med. 2017 Feb;5(2):2325967117690131 Authors: Korpershoek JV, de Windt TS, Hagmeijer MH, Vonk LA, Saris DB Abstract BACKGROUND: Meniscus damage can be caused by trauma or degeneration and is therefore common among patients of all ages. Repair or regeneration of the menisci could be of great importance not only for pain relief or regaining function but also to prevent degenerative disease and osteoarthritis. Current treatment does not offer consistent long-term improvement. Although preclinical research focusing on augmentation of meniscal tear repair and regeneration after meniscectomy is encouraging, clinical translation remains difficult. PURPOSE: To systematically evaluate the literature on in vivo meniscus regeneration and explore the optimal cell sources and conditions for clinical translation. We aimed at thorough evaluation of current evidence as well as clarifying the challenges for future preclinical and clinical studies. STUDY DESIGN: Systematic review. METHODS: A search was conducted using the electronic databases of MEDLINE, Embase, and the Cochrane Collaboration. Search terms included meniscus, regeneration, and cell-based. RESULTS: After screening 81 articles based on title and abstract, 51 articles on in vivo meniscus regeneration could be included; 2 additional articles were identified from the references. Repair and regeneration of the meniscus has been described by intra-articular injection of multipotent mesenchymal stromal (stem) cells from adipose tissue, bone marrow, synovium, or meniscus or the use of these cell types in combination with implantable or injectable scaffolds. The use of fibrochondrocytes, chondrocytes, and transfected myoblasts for meniscus repair and regeneration is limited to the combination with different scaffolds. The comparative in vitro and in vivo studies mentioned in this review indicate that the use of allogeneic cells is as successful as the use of autologous cells. In addition, the implantation or injection of cell-seeded scaffolds increased tissue regeneration and led to better structural organization compared with scaffold implantation or injection of a scaffold alone. None of the studies mentioned in this review compare the effectiveness of different (cell-seeded) scaffolds. CONCLUSION: There is heterogeneity in animal models, cell types, and scaffolds used, and limited comparative studies are available. The comparative in vivo research that is currently available is insufficient to draw strong conclusions as to which cell type is the most promising. However, there is a vast amount of in vivo research on the use of different types of multipotent mesenchymal stromal (stem) cells in different experimental settings, and good results are reported in terms of tissue formation. None of these studies compare the effectiveness of different cell-scaffold combinations, making it hard to conclude which scaffold has the greatest potential. PMID: 28321424 [PubMed - in process]Read more...