Mesenchymal stem cells (MSCs) can be isolated from several adult tissues, such as bone marrow, fat, and blood, and cultured in vitro for extensive propagation. These cells are multi-potent, and with proper biochemical or physical cues, they can differentiate into various connective tissue linage cells, such as osteoblast, chondrocyte, adipocyte, and tenocyte. Notably, transplanted allogeneic MSCs can regulate the activity of recipient’s immune cells to reduce the immune response. These unique properties make MSCs an attractive cell source for cell therapy and regenerative medicine applications.
Using MSCs to regenerate cartilage for tissue repair is a promising treatment to osteoarthritis (OA) or other cartilage defects. However, one of the challenges using MSCs for regenerative medicine is that the cells isolated from adult tissues are often composed of heterogeneous cell populations, and the heterogeneity increases the difficulty of using the cells for cartilage regeneration. Another challenge is that MSCs become aged and senescent after several cell passages in vitro culture, limiting the use for clinical applications. To overcome the challenges, we derive MSCs from human embryonic stem cells (hESCs) and study the potential of hESC-MSCs for cartilage regeneration. We compare the phenotype of hESC-MSCs with that of bone marrow-derived MSCs. Flow cytometry analysis shows that MSCs and hESC-MSCs express similar cell surface markers. In terms of the potential for chondrogenesis, the mRNA transcript levels of chondrocyte-related matrix proteins and transcription factors, such as collagens type II, IX, and X, aggrecan, and Sox9, are upregulated in MSCs compared to those in hESC-MSCs during chondrogenesis, suggesting that the current differentiation protocol more effectively induces MSCs into chondrocytes than hESC-MSCs, and an improved differentiation protocols should be developed to induce chondrogenesis of hESC-MSCs.
For cartilage tissue engineering applications, we have used a nanotechnology to fabricate a scaffold as a three-dimensional culture template for MSCs to regenerate cartilage. The unique scaffolding structure with ultra-fine fibers structurally similar to collagen fibrils has been shown to support MSC chondrogenesis and maintain chondrocyte phenotype. An in vivo animal model for testing cartilage repair shows that MSC-laden nanofiber-based engineered cartilage successfully repairs joint defects after 6 months. The regenerated tissue on the joint surface is able to carry out biomechanical function. Taken together, we have shown the potential of using stem cell and nanofabrication technologies to regenerate functional cartilage for cartilage treatment.
Professor Wan-Ju Li is the Principal Investigator of the Musculoskeletal Biology and Regenerative Medicine Laboratory at the University of Wisconsin-Madison in the United States of America. He is also an affiliated faculty member in Cellular and Molecular Biology Program, and Stem Cell and Regenerative Medicine Center. His research interests include stem cell, tissue engineering, nanobiomaterial, and skeletal biology. Professor Li is the member of International Society for Stem Cell Research, Orthopaedic Research Society, Tissue Engineering International and Regenerative Medicine Society, American Society for Cell Biology, and American Society for Bone and Mineral Research. He has published 45 papers, 9 book chapters, and more than 60 abstracts. Many of his papers have been highly cited, including a paper published in 2002 has received more than 1500 citations and 3 other papers have been cited more than 400 times each. He holds 3 patents in cartilage, intervertebral disc, and tendon/ligament applications. Professor Li has received Fellow Award for Research Excellence from National Institutes of Health, and Young Investigator Research Award from North American Spine Society, and Nontenure Faculty Award from 3M. Professor Li is the editor-in-chief of Nanomaterials and Tissue Regeneration. He also serves in the editorial board of PLoS One, BioMed Research International, American Journal of Stem Cells, Journal of Regenerative Medicine and Tissue Engineering, Formosan Journal of Musculoskeletal Disorders, and Journal of Biosensors and Bioelectronics.