Mesenchymal stem cell-based tissue engineering strategies for repair of articular cartilage (original) (raw)
Related papers
2016
Articular cartilage damage associated with joint trauma seldom heals and often leads to osteoarthritis (OA). Current treatment often fails to regenerate functional cartilage close to native tissue. We previously identified a migratory chondrogenic progenitor cell (CPC) population that responded chemotactically to cell death and rapidly repopulated the injured cartilage matrix, which suggested their potential for cartilage repair. To test that potential we filled experimental full thickness chondral defects with an acellular hydrogel containing SDF-1α. We expect that SDF-1α can increase the recruitment of CPCs, and then promote the formation of a functional cartilage matrix with chondrogenic factors. Fullthickness bovine chondral defects were filled with hydrogel comprised of fibrin and hyaluronic acid and containing SDF-1α. Cell migration was monitored, followed by chondrogenic induction. Regenerated tissue was evaluated by histology, immunohistochemistry, and scanning electron microscopy. Push-out tests were performed to assess the strength of integration between regenerated tissue and host cartilage. Significant numbers of progenitor cells were recruited by SDF-1α within 12 days. By 5 weeks chondrogenesis, repair tissue cell morphology, proteoglycan density and surface ultrastructure were similar to native cartilage. SDF-1α treated defects had significantly greater interfacial strength than untreated controls, and regenerated cartilage tissue has mechanical properties within the physiological range of normal cartilage. In addition to that, we developed a 3D bioprinting platform, which can directly print chondrocytes as well as CPCs to fabricated articular cartilage tissue in vitro, which can be iv used for implantation to treat larger cartilage defect. We successfully implanted the printed tissue into an osteochondral defect, and observed tissue repair after implantation. The regerated tissue has biochemical and mechanical properties within the physiological range of native articular cartilage. This st udy showed that, when CPC chemotaxis and chondrogenesis are stimulated sequentially, in situ full thickness cartilage regeneration and bonding of repair tissue to surrounding cartilage could occur without the need for cell transplantation from exogenous sources. This study also demonstrated the potential of using 3D bioprinting to engineer articular cartilage implants for repairing damaged cartilage. v PUBLIC ABSTRACT Knee injuries are very common among athletes, as well as people with active athletic life style. Articular cartilage is often subject to traumatic damage after knee injuries. Current clinical treatments to repair damaged cartilage are often complicated, costly and do not have satisfactory long-term success. Even after cartilage repair surgery, cartilage degeneration is often inevitable, and can lead to painful osteoarthritis. In this study, we first identified molecular factors to activate patients` own stem cells, known as chondrogenic progenitor cells (CPCs). CPCs once activated, can come out from surrounding healthy cartilage, and move into damaged area implanted with hydrogel, to develop into new cartilage. Different tests revealed that the new cartilage is mechanically as strong as normal cartilage with similar functions. In the second part of this study, we developed 3D bioprinting system to fabricated cartilage tissue as implants for treating patients with articular cartilage injuries. We made "biological ink" out the cartilage cells called chondrocytes, and pattern these cells into a cylindrical strand shape, in order to 3D print it into the desired shape. We then implanted the printed cartilage tissue to repair articular cartilage damage in an experimental model. The 3D bioprinted cartilage has similar structures as normal cartilage, as well as comparable mechanical strength as normal cartilage. This study pro vided new insights for articular cartilage repair combining engineering principles as well as biomedical mechanisms.
Applications of Mesenchymal Stem Cells in Cartilage Tissue Engineering- Part 1
Recent Patents on Regenerative Medicinee, 2011
Arthritic diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA) cause considerable pain, reduced mobility and significant disability among affected patients and present a major challenge to clinicians and basic scientists due to the limited inherent repair capacity of articular cartilage. The poor capacity of articular cartilage for self-repair is largely due to its avascular nature and has resulted in the development of a variety of surgical treatments including Autologous Chondrocyte Implantation (ACI) or Autologous Chondrocyte Transplantation (ACT), microfracture and mosaicplasty. Mesenchymal stem cells (MSCs) are multipotent progenitor cells with significant potential for chondrogenesis and new cartilage formation. Novel approaches using MSCs derived from bone marrow and adipose tissue have been proposed as alternatives to patient derived chondrocytes. In this paper we provide a scientific background to the biology of articular cartilage biology and its degeneration in arthritis. We also summarize some of the recent patents on applications of MSCs in articular cartilage tissue engineering and regenerative medicine for OA, RA and other joint diseases that involve cartilage degradation.
Arthritis & Rheumatism, 2006
Degenerative joint diseases such as osteoarthritis cause pain and compromise mobility, thus posing a significant disease burden. Articular cartilage, the loadbearing tissue of the joint, has limited potential for repair and regeneration. An attractive approach is to develop engineered cartilage constructs for the repair of large chondral defects (1). Cartilage tissue engineering requires 3 components: cells, scaffold, and environment. Adult stem cells, specifically mesenchymal stem cells (MSCs), are often considered a promising candidate cell source because of the ease with which they can be isolated and expanded and their chondrogenic differentiation capabilities. MSCs are isolated from many adult tissue types, such as bone marrow, skin, muscle, and trabecular bone, and are characterized by their ability to undergo extensive self-renewal in vitro and to assume multilineage differentiation, including osteogenesis, chondrogenesis, and adipogenesis (2). Commonly selected by differential substrate adhesion, MSCs exhibit surface epitopes such as Stro1 and CD105, although no MSC-specific molecular marker(s) have been identified. The chondrogenic activity of MSCs has been demonstrated in vitro in high-density pellet cultures treated with transforming growth factor  (TGF) (3). The appearance of a cartilage phenotype is accompanied by characteristic histologic features, the expression of cartilage-associated genes such as types II and IX collagen as well as aggrecan and dermatopontin, and the biosynthesis of sulfated proteoglycans. Translating the micro-scale cartilage formation by MSCs in vitro to larger-scale cartilage tissue engineering ex vivo and/or in vivo is a current challenge of musculoskeletal regenerative medicine.
Mesenchymal stem cells as a potential pool for cartilage tissue engineering
Annals of Anatomy - Anatomischer Anzeiger, 2008
Osteoarthritis (OA) resulting from trauma, degenerative or age-related disease presents a major clinical challenge due to the limited repair capacity of articular cartilage. This poor self-repair capacity of osteochondral defects has resulted in the development of a wide variety of new treatment approaches. Although the use of chondrocytes in applications of cartilage tissue engineering is still prevalent, concerns associated with donor-site morbidity, cell de-differentiation and the limited lifespan of these cells have brought the use of mesenchymal stem cells (MSCs) to the forefront of such applications. Therefore, in the last two decades MSCs have come into the focus of connective tissue engineering and regenerative medicine and have become increasingly sought after as an alternative cell source for improving well-established methods of osteochondrotic cartilage defect repair such as the Autologous Chondrocyte Transplantation method, but are also being tested as an ideal cell source in combination with newly developed implantable scaffolds or as a target/carrier cell in other new concepts of regenerative medicine. However, up to now, although in animal models MSCs have already shown significant potential for cartilage repair and novel approaches using MSCs as an alternative cell source to patient-derived chondrocytes are being tested, much more research is needed before feasible clinical application of MSCs becomes reality.
Cartilage Tissue Engineering: Towards a Biomaterial-Assisted Mesenchymal Stem Cell Therapy
Current Stem Cell Research & Therapy, 2009
Injuries to articular cartilage are one of the most challenging issues of musculoskeletal medicine due to the poor intrinsic ability of this tissue for repair. Despite progress in orthopaedic surgery, the lack of efficient modalities of treatment for large chondral defects has prompted research on tissue engineering combining chondrogenic cells, scaffold materials and environmental factors. The aim of this review is to focus on the recent advances made in exploiting the potentials of cell therapy for cartilage engineering. These include: 1) defining the best cell candidates between chondrocytes or multipotent progenitor cells, such as multipotent mesenchymal stromal cells (MSC), in terms of readily available sources for isolation, expansion and repair potential; 2) engineering biocompatible and biodegradable natural or artificial matrix scaffolds as cell carriers, chondrogenic factors releasing factories and supports for defect filling, 3) identifying more specific growth factors and the appropriate scheme of application that will promote both chondrogenic differentiation and then maintain the differentiated phenotype overtime and 4) evaluating the optimal combinations that will answer to the functional demand placed upon cartilage tissue replacement in animal models and in clinics. Finally, some of the major obstacles generally encountered in cartilage engineering are discussed as well as future trends to overcome these limiting issues for clinical applications.
Stem cell reviews, 2017
Large articular cartilage defects remain an immense challenge in the field of regenerative medicine because of their poor intrinsic repair capacity. Currently, the available medical interventions can relieve clinical symptoms to some extent, but fail to repair the cartilaginous injuries with authentic hyaline cartilage. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stem/progenitor cells with or without scaffolds. Mesenchymal stem/progenitor cells are promising graft cells for tissue regeneration, but the most suitable source of cells for cartilage repair remains controversial. The tissue origin of mesenchymal stem/progenitor cells notably influences the biological properties and therapeutic potential. It is well known that mesenchymal stem/progenitor cells derived from synovial joint tissues exhibit superior chondrogenic ability compared with those derived from non-joint tissues; thus, these cell populations are...
A Review Study: Using Stem Cells in Cartilage Regeneration and Tissue Engineering
Articular cartilage, the load-bearing tissue of the joint, has limited repair and regeneration ability. The scarcity of treatment modalities for large chondral defects has motivated researchers to engineer cartilage tissue constructs that can meet the functional demands of this tissue in vivo. Cartilage tissue engineering requires 3 components: cells, scaffold, and environment. Owning to their easy isolation, expansion, and multilineage differentiation, adult stem cells, specifically multipotential mesenchymal stem cells, are considered the proper candidate for tissue engineering. Successful outcome of cell-based cartilage tissue engineering ultimately depends on the proper differentiation of stem cells into chondrocytes and assembly of the appropriate cartilaginous matrix to achieve the load-bearing capabilities of the natural articular cartilage. Furthermore, multiple parameters such as growth factors, signaling molecules, and physical conditions must be considered. Adult mesenchymal stem-cell-based tissue engineering is a promising technology for creating a transplantable cartilage replacement to improve joint function.