Table 1.
Alternative cell sources for ACI and their cultivation demand.
| Cell type | Exogenous stimuli in cultivation system | Epitope marker | Marker (genetic factors) for chondrogenic transdifferentiation | Clinical application | Reference | |
|---|---|---|---|---|---|---|
| Chondrocytes | AC | BMP-2/4, TGF-β1 | CD44/54/73+ CD164- |
no need | Most widely used, potential secondary degeneration during extraction | Makris et al. (2015) [2] Pelttari et al. (2017) [18] Campbell et al. (2012) [26] |
| NC | TGF-β1, FGF-2, IGF-1, GDF-5 | Hox (+) | Generate hyaline-like cartilage, capable of self-renewal | |||
| MSC | BMSC | TGF-β1, ascorbic acid, dexamethasone, sodium pyruvate, insulin–transferrin–selenium | CD44/73/29/90/105 (+) CD11/14/31/34/45 (−) |
Sox-9(+) FOXO3A (+) Hoxa2 (−) HOXD9 & HOXD13(+) ZNF145 (+) |
Bone marrow aspiration is painful, yielding small amount of MSC | Almalki and Agrawal (2017) [24] Perdisa et al. (2015) [27] |
| ADSC | Easy to isolate with large quantities; prone to misdifferentiation | |||||
| SSC | TGF-β1, Indian hedgehog (inducing hypertrophic chondrocytes) | PDPN (+); CD146 (−); CD73 (+); CD164 (+) | Sox-9(+) Runx2(−) PPARγ2(−) |
Newly identified, have not been applied clinically | Bianco & Robey (2015) [28] Chan et al. (2018) [27] |
|
| Pluripotent stem cells | ESC | Co-culture with mature chondrocytes | SSEA-3 (+) CD324/90/117/326 (+) |
Sox-9(+) Runx2(−) OSX (−) |
Cannot be extracted autologously; potential teratoma induction and immune response | Jukes, Blitterswijk and Boer (2010) [29] |
| iPSC | TGF-β1, Co-culture with mature chondrocytes | TRA-1-60 (+) TRA-1-81 (+) |
Teratoma induction and immune response due to incomplete reprogramming | Tapia & Schöler (2016) [30] | ||
AC = articular chondrocyte; ADSC = adipose-derived mesenchymal stem cell; BMSC = bone marrow–derived mesenchymal stem cells; BMP = bone morphogenic protein; ESC = embryonic stem cell; FGF = fibroblast growth factor; GDF = growth differentiation factor; IGF = insulin-like growth factor; iPSC = induced pluripotent stem cell; MSC = mesenchymal stem cell; NC = nasal chondrocyte; PPARγ2 = peroxisome proliferator–activated receptor γ2; Sox-9 = SRY-related high mobility group-box gene 9; SSC = skeletal stem cell; TGF = transforming growth factor; ZNF145 = zinc-finger protein 145; (+) = upregulation; (−) = downregulation