Osteoarthritis Stem Cell Treatment

Stem Cell Treatment and Osteoarthritis at SIRM

What is Osteoarthritis ?

Stem Cell Treatment for Osteoarthritis Knee

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.

Stem Cell Injections for Osteoarthritis

Stem Cell Treatment for Osteoarthritis

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:

Related Articles Notch ligand Jagged1 promotes mesenchymal stromal cell-based cartilage repair. Exp Mol Med. 2018 09 21;50(9):126 Authors: Sun J, Luo Z, Wang G, Wang Y, Wang Y, Olmedo M, Morandi MM, Barton S, Kevil CG, Shu B, Shang X, Dong Y Abstract Placenta-derived mesenchymal stromal cells (PMSCs) provide a promising cell source for tissue regeneration. However, rapid induction of PMSC chondrogenic differentiation during therapeutic transplantation remains extremely challenging. Here we undertook a study to determine if Notch inhibition by soluble Jagged1 (JAG1) peptides could be utilized to accelerate PMSC-induced cartilage regeneration in a mouse post-traumatic osteoarthritis (PTOA) model. Our results showed that treatment of PMSCs with soluble JAG1 significantly enhanced chondrogenesis in culture as shown by increased alcian blue staining and decreased Notch target Hes1 expression when compared to those in lgG-treated control cells. Importantly, significantly enhanced cartilage formation and decreased joint inflammation were observed when JAG1-treated PMSCs were injected into mouse PTOA knee joints. Finally, in vivo cell tracing showed that more JAG1-treated PMSCs remained in knee joint tissues and that JAG1-treated PMSCs exhibited greater PMSC chondrogenic differentiation than lgG-treated control PMSCs at 4 weeks after injection. These data indicate that transient Notch inhibition by soluble JAG1 could be used to enhance PMSC survival and chondrogenic differentiation, thereby increasing the therapeutic potential of PMSCs for cartilage regeneration. PMID: 30242147 [PubMed - indexed for MEDLINE]
Related Articles Single-Cell Profiles and Clinically Useful Properties of Human Mesenchymal Stem Cells of Adipose and Bone Marrow Origin. Am J Sports Med. 2019 May 17;:363546519848678 Authors: Zhou W, Lin J, Zhao K, Jin K, He Q, Hu Y, Feng G, Cai Y, Xia C, Liu H, Shen W, Hu X, Ouyang H Abstract BACKGROUND: Mesenchymal stem cells (MSCs) can be isolated from various tissues and can present themselves as a promising cell source for cell-based therapies. Although adipose- and bone marrow-derived mesenchymal stem cells have already been used in a considerable number of clinical trials for osteoarthritis treatment, systematic analyses from single- to bulk-cell resolution as well as clinical outcomes of these 2 MSCs are still insufficient. PURPOSE: To explore the characteristics and differences of adipose-derived stem cells (ADSCs) and bone marrow MSCs (BMSCs) at single- and bulk-cell levels, to study the clinical outcomes of these 2 cells on the treatment of osteoarthritis, and to provide potential guidance on the more precise clinical application of these MSCs. STUDY DESIGN: Controlled laboratory study and meta-analysis. METHODS: Same donor-derived ADSCs and BMSCs were isolated and cultured. Single- and bulk-cell assays were used to identify the characteristics of these 2 cells. Meta-analysis of clinical trials was done to compare the clinical therapeutic effects in osteoarthritis treatment with ADSCs and BMSCs. RESULTS: Single-cell RNA sequencing analysis showed that the population of ADSCs showed lower transcriptomic heterogeneity when compared with BMSCs. Additionally, as compared with BMSCs, ADSCs were less dependent on mitochondrial respiration for energy production. Furthermore, ADSCs had a lower expression level of human leukocyte antigen class I antigen and higher immunosuppression capacity when compared with the BMSC population. Meta-analysis of current clinical trials of osteoarthritis treatment with MSCs consistently showed that ADSCs are more stable than BMSCs in their therapeutic effect. CONCLUSION: These results provide basic biological insights into human ADSCs and BMSCs at the single-cell resolution. Findings indicated that ADSCs may be a more controllable stem cell source, may be more adaptable to surviving in the hypoxic articular cavity niche, and may exhibit superiority in regulating inflammation. Based on the meta-analysis results of the different characteristics of ADSCs and BMSCs, ADSCs were implicated as being a better cell source for osteoarthritis treatment. CLINICAL RELEVANCE: These results guide a more precise clinical application of adipose and bone marrow mesenchymal stem cells. PMID: 31100005 [PubMed - as supplied by publisher]
Related Articles Mesenchymal Stem Cell Treatment of Osteoarthritis. Vet Comp Orthop Traumatol. 2019 May;32(3):v Authors: Johnson KA PMID: 31100764 [PubMed - in process]

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