Adam Olson

 Introduction. Damage to articular cartilage often results from physical trauma or age-related abrasion.⁴ In all cases, however, it leads to constant pain and functional limitations, and can predispose individuals to osteoarthritis.^1,2,4 Once damaged, the poorly vascularized tissue is slow to repair, and often heals improperly.^1-4 Many of the current treatments are centered on slowing disease progression and managing pain, but studies show that mesenchymal stem cells have the potential to promote the actual regeneration of damaged articular cartilage. By analyzing the external signals that promote progenitor stem cells to differentiate down specific cell lineages, researchers are have successfully caused adipose-derived mesenchymal stem cells (AD-MSCs) to differentiate into articular cartilage ex vivo.^2,4,7 This study focuses on comparing intra-articular injections of AD-MSCs with micro-scaffolding and hyaluronan to promote stem cell differentiation in vivo.^3,6,8,10 Methods. Intra-articular Injections: 18 patients with osteoarthritis were randomised into 3 dose-escalated cohorts for arthroscopy and AD-MSCs injections into the knee. Patients were evaluated clinically at one month intervals following injection. Second look arthroscopy and MRI were performed at 6 months.³ Adherence and Proliferation: Ultra low adherence 96-well plates were plugged with cartilage discs and MSCs were seeded, suspended in either control or hyaluronan media (0.5–5mg/mL HA). Cells in each media were counted after 24 hours for adherence and after three days for proliferation.¹⁰ In a separate test, bone marrow and adipose derived MSCs were seeded onto Chondro-Gide and Alpha Chondro Shield micro-scaffolding. Viable stem cells were counted after 24 hours, and again after one, two, and four week intervals.⁸ Results. Intra-articular injection of AD-MSCs did not lead to differentiation or proliferation of injected cells on its own.³ Instead, injected MSCs upregulated endogenous cells leading to an increase in healing of damaged tissues, increase in overall function of the joint, and decrease in pain on movement for patients receiving treatment.^3,6 In contrast, the use of Chondro-gide micro-scaffolding and the priming of AD-MSCs with hyaluronan both led to greater adherence of implanted stem cells to ex vivo cartilage as well as increased proliferation after adherence.^8,10 Conclusion. The ability to influence AD-MSCs to differentiate down specific pathways towards chondrocyte formation was an important step in the successful regeneration of articular cartilage in vitro.^2,4,7,8,10 Micro-scaffolding and hyaluronan priming show additional potential in the transition from ex vivo to in vivo regeneration of articular cartilage. With additional study, AD-MSCs may finally lead to effective medical interventions for joint damage and osteoarthritis.

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2. Guzzo, Rosa M., and Michael B. O’Sullivan. “Human Pluripotent Stem Cells: Advances in Chondrogenic Differentiation and Articular Cartilage Regeneration.” Current Molecular Biology Reports 2.3 (2016): 113-22. Web. 22 Mar. 2017.
3. Jo, Chris Hyunchul, et al. “Intra-Articular Injection of Mesenchymal Stem Cells for the Treatment of Osteoarthritis of the Knee: A Proof-of-Concept Clinical Trial.” Stem Cells 32.5 (2014): 1254-266. Web. 22 Mar. 2017.
4. Wu, Ling, et al. “Regeneration of articular cartilage by adipose tissue derived mesenchymal stem cells: Perspectives from stem cell biology and molecular medicine.” Journal of Cellular Physiology 228.5 (2013): 938-44. Web. 22 Mar. 2017.
5. Bari CD, Dell’accio F, Luyten FP. Failure of in vitro-differentiated mesenchymal stem cells from the synovial membrane to form ectopic stable cartilage in vivo. Arthritis & Rheumatism. 2004;50(1):142-150.
6. Black LL, et al. Effect of Adipose-Derived Mesenchymal Stem and Regenerative Cells on Lameness in Dogs with Chronic Osteoarthritis of the Coxofemoral Joings: a Randomized, Double-Blinded, Multicenter, Controlled Trial. Veterinary Therapeutics. 2007;8(4):272-284.
7. Casado-Díaz A, Anter J, Müller S, Winter P, Quesada-Gómez JM, Dorado G. Transcriptomic Analyses of Adipocyte Differentiation From Human Mesenchymal Stromal-Cells (MSC). Journal of Cellular Physiology. 2016;232(4):771-784.
8. Kohli N, Wright KT, Sammons RL, Jeys L, Snow M, Johnson WEB. An In Vitro Comparison of the Incorporation, Growth, and Chondrogenic Potential of Human Bone Marrow versus Adipose Tissue Mesenchymal Stem Cells in Clinically Relevant Cell Scaffolds Used for Cartilage Repair. Cartilage. 2015;6(4):252-263.
9. Rey-Rico A, Reinecke J, Wehling P, Cucchiarini M, Madry H. Effects of exosomes upon the metabolic activities of human osteoarthritic articular cartilage in situ. Osteoarthritis and Cartilage. 2015;23.
10. Succar P, Medynskyj M, Breen EJ, Batterham T, Molloy MP, Herbert BR. Priming Adipose-Derived Mesenchymal Stem Cells with Hyaluronan Alters Growth Kinetics and Increases Attachment to Articular Cartilage. Stem Cells International. 2016;2016:1-13.