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Mesenchymal regenerative medicine therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy – a review

Osteoarthritis, Research StudiesBy Regenerative Medicine Therapy Clinic January 28, 2019

Osteoarthritis is a leading cause of pain and disability across the world. With an aging population its prevalence is likely to further increase. Current accepted medical treatment strategies are aimed at symptom control rather than disease modification. Surgical options including joint replacement are not without possible significant complications. A growing interest in the area of regenerative medicine, led by an improved understanding of the role of mesenchymal regenerative medicines in tissue homeostasis and repair, has seen recent focused efforts to explore the potential of regenerative medicine therapies in the active management of symptomatic osteoarthritis.
https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-016-1085-9
Julien Freitag, Dan Bates, Richard Boyd, Kiran Shah, Adele Barnard, Leesa Huguenin and Abi Tenen

Cartilage Regeneration in Osteoarthritic Patients by a Composite of Allogeneic Umbilical Cord Blood‐Derived Mesenchymal Regenerative Medicines and Hyaluronate Hydrogel: Results from a Clinical Trial for Safety and Proof‐of‐Concept with 7 Years of Extended Follow‐Up

Osteoarthritis, Research StudiesBy Regenerative Medicine Therapy Clinic January 28, 2019

Few methods are available to regenerate articular cartilage defects in patients with osteoarthritis. We aimed to assess the safety and efficacy of articular cartilage regeneration by a novel medicinal product composed of allogeneic human umbilical cord blood‐derived mesenchymal regenerative medicines (hUCB‐MSCs). Patients with Kellgren‐Lawrence grade 3 osteoarthritis and International Cartilage Repair Society (ICRS) grade 4 cartilage defects were enrolled in this clinical trial. The regenerative medicine‐based medicinal product (a composite of culture‐expanded allogeneic hUCB‐MSCs and hyaluronic acid hydrogel [Cartistem]) was applied to the lesion site.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442809/

Mesenchymal regenerative medicines for cartilage regeneration in osteoarthritis

Osteoarthritis, Research StudiesBy Regenerative Medicine Therapy Clinic January 28, 2019

Osteoarthritis (OA) is a slowly progressive disease where cartilage of the synovial joint degenerates. It is most common in the elderly where patients experience pain and reduce physical activity. In combination with lack of conventional treatment, patients are often left with no other choices than arthroplasty. Over the last years, multipotent stromal cells have been used in efforts to treat OA. Mesenchymal stem/progenitor cells (MSCs) are stromal cells that can differentiate into bone, fat, and cartilage cells. They reside within bone marrow and fat.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605352/
Baldur Kristjánsson and Sittisak Honsawek

Intra‐Articular Injection of Mesenchymal Regenerative Medicines for the Treatment of Osteoarthritis of the Knee: A Proof‐of‐Concept Clinical Trial

Knee Research, Osteoarthritis, Research StudiesBy Regenerative Medicine Therapy Clinic January 28, 2019

Mesenchymal regenerative medicines (MSCs) are known to have a potential for articular cartilage regeneration. However, most studies focused on focal cartilage defect through surgical implantation. For the treatment of generalized cartilage loss in osteoarthritis, an alternative delivery strategy would be more appropriate. The purpose of this study was to assess the safety and efficacy of intra‐articular injection of autologous adipose tissue derived MSCs (AD‐MSCs) for knee osteoarthritis. We enrolled 18 patients with osteoarthritis of the knee and injected AD MSCs into the knee. The phase I study consists of three dose‐escalation cohorts; the low‐dose (1.0 × 107 cells), mid‐dose (5.0 × 107), and high‐dose (1.0 × 108) group with three patients each.
https://stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/stem.1634
Chris Hyunchul Jo, Young Gil Lee, Won Hyoung Shin, Hyang Kim, Jee Won Chai, Eui Cheol Jeong, Ji Eun Kim, Hackjoon Shim, Ji Sun Shin, Il Seob Shin, Jeong Chan Ra, Sohee Oh, and Kang Sup Yoon

Mesenchymal regenerative medicines in osteoarthritis

Osteoarthritis, Research StudiesBy Regenerative Medicine Therapy Clinic January 28, 2019

Accumulating evidence indicates that every tissue contains regenerative medicines. Our understanding of the biology of regenerative medicines reveals that these cell populations have a critical role in the homeostasis and repair of tissues. Besides the local regenerative medicine niches, additional compartments in the body such as the bone marrow may serve as reservoirs for regenerative medicine populations. On more extensive tissue damage, and guided by local repair responses, “reparative” cell populations are mobilized from more distant regenerative medicine reservoirs and migrate to the site of injury, thereby contributing in many aspects of local tissue repair.
https://journals.lww.com/co-rheumatology/Abstract/2004/09000/Mesenchymal_stem_cells_in_osteoarthritis.19.aspx
Frank P. Luyten

Inhibition of TAK1 and/or JAK Can Rescue Impaired Chondrogenic Differentiation of Human Mesenchymal Regenerative Medicines in Osteoarthritis-Like Conditions

Osteoarthritis, Research StudiesBy Regenerative Medicine Therapy Clinic January 28, 2019

Objective: To rescue chondrogenic differentiation of human mesenchymal regenerative medicines (hMSCs) in osteoarthritic conditions by inhibition of protein kinases.
Methods: hMSCs were cultured in pellets. During early chondrogenic differentiation, these were exposed to osteoarthritic synovium-conditioned medium (OAS-CM), combined with the Janus kinase (JAK)-inhibitor tofacitinib and/or the transforming growth factor β-activated kinase 1 (TAK1)-inhibitor oxozeaenol. To evaluate effects on chondrogenesis, the glycosaminoglycan (GAG) content of the pellets was measured at the time that chondrogenesis was manifest in control cultures.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137338/
Henk M. van Beuningen, PhD, Marloes L. de Vries-van Melle, MSc, Elly L. Vitters, MSc, Wim Schreurs, MD, PhD, Wim B. van den Berg, PhD, Gerjo J.V.M. van Osch, PhD, and Peter M. van der Kraan, PhD

Mesenchymal regenerative medicines for cartilage repair in osteoarthritis

Osteoarthritis, Research StudiesBy Regenerative Medicine Therapy Clinic January 28, 2019

Osteoarthritis (OA) is a degenerative disease of the connective tissue and progresses with age in the older population or develops in young athletes following sports-related injury. The articular cartilage is especially vulnerable to damage and has poor potential for regeneration because of the absence of vasculature within the tissue. Normal load-bearing capacity and biomechanical properties of thinning cartilage are severely compromised during the course of disease progression. Although surgical and pharmaceutical interventions are currently available for treating OA, restoration of normal cartilage function has been difficult to achieve.
https://stemcellres.biomedcentral.com/articles/10.1186/scrt116
Pawan K Gupta, Anjan K Das, Anoop Chullikana and Anish S Majumdar