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Table 2 Therapeutic potentials and limitations of cell based therapies in osteoarthritis

From: Therapeutic potential of mesenchymal stem cell based therapy for osteoarthritis

Cellular therapy Advantages Shortcomings References
Autologous chondrocyte implantation (ACI) Success rate of 76–86 %; FDA approved; uses autologous cells; reduces pain; some instances of new production of durable cartilage-like tissue; MACI reduces graft hypertrophy Requires two costly surgical procedures; less than 22 % chondrocytes successfully isolated; proliferation of chondrocytes decreases with patient age; chondrocytes often de-differentiate from type II collagen and lose capacity; specific ECM environment is required to keep chondrocytes differentiated, and ECM secretion capacity is lost with increasing chondrocyte age; periosteal grafts can detach, delaminate, and hypertrophy; uneven distribution of cells reported; often no clinical/radiographical changes [924]
Embryonic stem cells (ESCs) Can undergo self-renewal and are pluripotent; can differentiate into chondrocytes; unlimited proliferative potential; induce cartilage repair in animal models Risk for teratoma formation, tumorgenicity, and immunogenicity; often require mouse fibroblasts to support cell growth, limiting human application; ESCs will likely never be used due to their ethically controversial nature; possibility of heterogeneous population of cells upon injection in patient; difficult to obtain large cell population of only chondrocytes [15, 2531]
Induced pluripotent stem cells (iPSCs) Can undergo self-renewal and are pluripotent; unlimited proliferative potential; can differentiate into cartilage; can be derived from human chondrocytes and differentiated into chondrocytes; autologous source, which means immune rejection is less likely than in ESCs Must be reprogrammed to differentiate into chondrocytes, which can be very difficult; risk for teratoma formation, tumorgenicity, and immunogenicity; difficult to obtain a uniform cell population; often obtain low yield of target cells; mechanisms poorly understood; cells retain epigenetic memory of original cell [15, 25, 26, 29, 3133]
Mesenchymal stem cells (MSCs) Can undergo high rates of proliferation; can differentiate into chondrocytes; have immunosuppressive actions, privileged properties, anti-inflammatory effects, and pro-regenerative properties; have the ability to recruit other natural chondrocytes in patient tissue; very low risk for teratoma formation; well documented and studied; easy to isolate and expand; don’t require extensive reprogramming; cells are tissue specific and can come from a variety of autologous sources; have demonstrated significant cartilage improvement and patient improvement; can migrate to site of injury and release healing cytokines Limited proliferation and differentiation potential in comparison to pluripotent stem cells; tissue specific morphology; their immunomodulative ability can cause problems; cells can be of heterogeneous population and difficult to classify; more randomized control trials are needed to better understand patient improvements [15, 19, 20, 26, 31, 3336]