In Vivo Formation of Stable Hyaline Cartilage by Naïve Human Bone Marrow Stromal Cells with Modified Fibrin Microbeads

• Published in: Stem cells translational medicine Vol. 8; no. 6; pp. 586 - 592
• Main Authors: Kuznetsov, Sergei A., Hailu‐Lazmi, Astar, Cherman, Natasha, Castro, Luis F., Robey, Pamela G., Gorodetsky, Raphael
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.06.2019; Oxford University Press
• Subjects: Animals; Autografts; Bone marrow; Bone marrow stromal cells; Cartilage (articular); Cartilage diseases; Cartilage formation; Cell Differentiation; Chondrocytes; Chondrogenesis; Collagen; Data analysis; Defects; Extracellular matrix; Fibrin; Fibrin - chemistry; Fibrin microbeads; Human subjects; Humans; Hyaline Cartilage - cytology; Hyaline Cartilage - metabolism; Hyaluronic acid; Hyaluronic Acid - chemistry; Hypertrophy; Immunocompromised Host; In vivo implantation; Laboratory animals; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mesenchyme; Mice; Microspheres; Osteoarthritis; Pediatrics; Stem cell transplantation; Stem cells; Stromal cells; Studies; Tissue Engineering; Tissue Engineering and Regenerative Medicine; Tissue Scaffolds - chemistry; Transplantation, Heterologous; Transplants & implants; Cartilage formation; Fibrin microbeads; Bone marrow stromal cells; In vivo implantation
• ISSN: 2157-6564; 2157-6580; 2157-6580
• DOI: 10.1002/sctm.18-0129

Osteoarthritic and other types of articular cartilage defects never heal on their own. Medicinal and surgical approaches are often ineffective, and the supply of autologous chondrocytes for tissue engineering is very limited. Bone marrow stromal cells (BMSCs, also known as bone marrow‐derived mesenchymal stem cells) have been suggested as an adequate cell source for cartilage reconstruction. However, the majority of studies employing BMSCs for cartilage tissue engineering have used BMSCs predifferentiated into cartilage prior to implantation. This strategy has failed to achieve formation of stable, hyaline‐like cartilage, resistant to hypertrophy in vivo. We hypothesized that in vitro predifferentiation of BMSCs is not necessary when cells are combined with an adequate scaffold that supports the formation of stable cartilage in vivo. In this study, naïve (undifferentiated) human BMSCs were attached to dehydrothermally crosslinked stable fibrin microbeads (FMBs) without and with other scaffolds and implanted subcutaneously into immunocompromised mice. Optimal formation of abundant, hypertrophy‐resistant, ectopic hyaline‐like cartilage was achieved when BMSCs were attached to FMBs covalently coated with hyaluronic acid. The cartilage that was formed was of human origin and was stable for at least 28 weeks in vivo. Stem Cells Translational Medicine 2019;8:586–592 Naïve (undifferentiated) human bone marrow stromal cells were attached to fibrin microbeads covalently coated with hyaluronic acid and implanted subcutaneously into immunocompromised mice. After 28 weeks in vivo, the constructs were white, large, glossy, and hard (inset). Abundant, nonhypertrophic, hyaline‐like cartilage of human origin was formed. Green scale bar = 5 mm; black scale bar = 1,000 μm.