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

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

[9–24]

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, 25–31]

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, 31–33]

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, 33–36]