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 Strenuous running exacerbates knee cartilage erosion induced by low amount of mono-iodoacetate in rats. BMC Musculoskelet Disord. 2017 Jan 25;18(1):36 Authors: Saito R, Muneta T, Ozeki N, Nakagawa Y, Udo M, Yanagisawa K, Tsuji K, Tomita M, Koga H, Sekiya I Abstract BACKGROUND: It is still debated whether strenuous running in the inflammatory phase produces beneficial or harmful effect in rat knees. We examined (1) the dropout rate of rats during a 30-km running protocol, (2) influences of strenuous running and/or low amounts of mono-iodoacetate injection on cartilage, and (3) the effect of strenuous running on synovitis. METHODS: Rats were forced to run 30 km over 6 weeks and the dropout rate was examined. One week after 0.1 mg mono-iodoacetate was injected into the right knee, rats were forced to run either 15 km or not run at all over 3 weeks, after which knee cartilage was evaluated. Synovium at the infrapatellar fat pad was also examined histologically. RESULTS: Even though all 12 rats run up to 15 km, only 6 rats completed 30 km of running. Macroscopically, 0.1 mg mono-iodoacetate induced erosion at the tibial cartilage irrespective of 15 km of running. Histologically, 0.1 mg mono-iodoacetate induced loss of cartilage matrix in the tibial cartilage, and an additional 15 km of strenuous running significantly exacerbated the loss. Synovitis caused by mono-iodoacetate improved after running. CONCLUSIONS: Only 50% of rats completed 30 km of running because of foot problems. Strenuous running further exacerbated tibial cartilage erosion but did not influence synovitis induced by mono-iodoacetate. PMID: 28122526 [PubMed - indexed for MEDLINE]
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Related Articles Genome Engineering of Stem Cells for Autonomously Regulated, Closed-Loop Delivery of Biologic Drugs. Stem Cell Reports. 2017 May 09;8(5):1202-1213 Authors: Brunger JM, Zutshi A, Willard VP, Gersbach CA, Guilak F Abstract Chronic inflammatory diseases such as arthritis are characterized by dysregulated responses to pro-inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α). Pharmacologic anti-cytokine therapies are often effective at diminishing this inflammatory response but have significant side effects and are used at high, constant doses that do not reflect the dynamic nature of disease activity. Using the CRISPR/Cas9 genome-engineering system, we created stem cells that antagonize IL-1- or TNF-α-mediated inflammation in an autoregulated, feedback-controlled manner. Our results show that genome engineering can be used successfully to rewire endogenous cell circuits to allow for prescribed input/output relationships between inflammatory mediators and their antagonists, providing a foundation for cell-based drug delivery or cell-based vaccines via a rapidly responsive, autoregulated system. The customization of intrinsic cellular signaling pathways in stem cells, as demonstrated here, opens innovative possibilities for safer and more effective therapeutic approaches for a wide variety of diseases. PMID: 28457885 [PubMed - indexed for MEDLINE]
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Articular Cartilage Aging-Potential Regenerative Capacities of Cell Manipulation and Stem Cell Therapy. Int J Mol Sci. 2018 Feb 22;19(2): Authors: Krajewska-Włodarczyk M, Owczarczyk-Saczonek A, Placek W, Osowski A, Wojtkiewicz J Abstract Changes in articular cartilage during the aging process are a stage of natural changes in the human body. Old age is the major risk factor for osteoarthritis but the disease does not have to be an inevitable consequence of aging. Chondrocytes are particularly prone to developing age-related changes. Changes in articular cartilage that take place in the course of aging include the acquisition of the senescence-associated secretory phenotype by chondrocytes, a decrease in the sensitivity of chondrocytes to growth factors, a destructive effect of chronic production of reactive oxygen species and the accumulation of the glycation end products. All of these factors affect the mechanical properties of articular cartilage. A better understanding of the underlying mechanisms in the process of articular cartilage aging may help to create new therapies aimed at slowing or inhibiting age-related modifications of articular cartilage. This paper presents the causes and consequences of cellular aging of chondrocytes and the biological therapeutic outlook for the regeneration of age-related changes of articular cartilage. PMID: 29470431 [PubMed - in process]
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