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 Autologous Matrix-Induced Chondrogenesis (AMIC) and AMIC Enhanced by Autologous Concentrated Bone Marrow Aspirate (BMAC) Allow for Stable Clinical and Functional Improvements at up to 9 Years Follow-Up: Results from a Randomized Controlled Study. J Clin Med. 2019 Mar 21;8(3): Authors: de Girolamo L, Schönhuber H, Viganò M, Bait C, Quaglia A, Thiebat G, Volpi P Abstract The aims of the study were to evaluate long-term outcomes after autologous matrix-induced chondrogenesis (AMIC) in the treatment of focal chondral lesions and to assess the possible improvements given by the combination of this technique with bone marrow aspirate concentrate (BMAC). Twenty-four patients (age range 18⁻55 years) affected by focal knee chondral lesions were treated with standard AMIC or AMIC enhanced by BMAC (AMIC+). Pain (Visual Analogue Scale (VAS)) and functional scores (Lysholm, International Knee Documentation Committee (IKDC), Tegner, Knee injury and Osteoarthritis Outcome Score (KOOS)) were collected pre-operatively and then at 6, 12, 24, 60, and 100 months after treatment. Magnetic resonance imaging (MRI) evaluation was performed pre-operatively and at 6, 12, and 24 months follow-ups. Patients treated with AMIC+ showed higher Lysholm scores (p = 0.015) and lower VAS (p = 0.011) in comparison with patients in the standard AMIC group at the 12 months follow-up. Both treatments allowed for functional and pain improvements with respect to pre-operative levels lasting up to 100 months. MRI revealed consistent cartilage repair at 24 months in both groups. This study shows that AMIC and AMIC+ are effective treatments for focal chondral lesions with beneficial effect lasting up to 9 years. AMIC+ allows for faster recovery from injury, and is thus more indicated for patients requiring a prompt return to activity. Level of evidence: II, randomized controlled trial in an explorative cohort. PMID: 30901900 [PubMed]
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Related Articles Chitosan-based composite bilayer scaffold as an in vitro osteochondral defect regeneration model. Biomed Microdevices. 2019 Mar 25;21(2):34 Authors: Erickson AE, Sun J, Lan Levengood SK, Swanson S, Chang FC, Tsao CT, Zhang M Abstract Prolonged osteochondral tissue damage can result in osteoarthritis and decreased quality of life. Multiphasic scaffolds, where different layers model different microenvironments, are a promising treatment approach, yet stable joining between layers during fabrication remains challenging. Here, a bilayer scaffold for osteochondral tissue regeneration was fabricated using thermally-induced phase separation (TIPS). Two distinct polymer solutions were layered before TIPS, and the resulting porous, bilayer scaffold was characterized by seamless interfacial integration and a mechanical stiffness gradient reflecting the native osteochondral microenvironment. Chitosan is a critical component of both scaffold layers to facilitate cell attachment and the formation of polyelectrolyte complexes with other biologically relevant natural polymers. The articular cartilage region was optimized for hyaluronic acid content and stiffness, while the subchondral bone region was defined by higher stiffness and osteoconductive hydroxyapatite content. Following co-culture with chondrocyte-like (SW-1353 or mesenchymal stem cells) and osteoblast-like cells (MG63), cell proliferation and migration to the interface along with increased gene expression associated with relevant markers of osteogenesis and chondrogenesis indicates the potential of this bilayer scaffold for osteochondral tissue regeneration. PMID: 30906951 [PubMed - in process]
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