Stem Cells International

Review Article

Advances in Regulatory Strategies of Differentiating Stem Cells towards Keratocytes

Table 2

Biochemical stimulation induces keratocyte differentiation.


Stem cells	Treatments	Effects

hMSCs	KCM	Spindle shaped; upregulated gene expression of keratocyte markers (KERA and ALDH1A1); downregulated expression of fibrotic marker (α-SMA) [27]
	KCM+AM	Dendritic or stellate morphology; upregulated gene expression of keratocyte markers (KERA and ALDH1A1); downregulated expression of fibrotic marker (α-SMA) [27]
	KCM+IGFBP2	Upregulated gene expression of keratocyte markers (KERA, LUM, and ALDH1A1) and downregulated expression of fibrotic marker (α-SMA) [38]
hCSSCs	FGF-2	Keratocyte-like morphology; barely no expression of myofibroblastic marker (α-SMA); increased protein and gene expression of keratocytes (KERA, LUM, ALDH3A1); decreased protein and gene expression of stem cells (Paired Box Gene 6 (Pax6), N-cadherin) [57]
	TGF-β3	Upregulated gene expression of keratocyte markers (KERA, beta-1,3-N-acetylglucosaminyltransferase 7 (B3GnT7), CHST6) [53]
	FGF-2+TGF-β3	Upregulated gene expression of keratocyte markers (KERA, B3GnT7, CHST6) [53]
ASCs	KDM¹+RA	Upregulated gene expression of keratocyte markers (KERA, ALDH3A1, LUM, decorin); higher acid sulfated glycosaminoglycans’ secretion; decreased expression of fibrotic marker (α-SMA) [2]
LBSCs	KDM²	Decreased expression of the stem cell genes (adenosine triphosphate-binding cassette G2 (ABCG2) and Nestin); increased gene expression of keratocyte markers (ALDH3A1, aquaporin1 (AQP1), KERA, and prostaglandin D2 synthase); secretion of ECM [30]
hPDLSCs	KDM²	Upregulated gene expression of keratocyte markers (LUM, KERA, ALDH3A1, ALDH1A1, COL I, COL V, COL III, COL VI) [7]

KCM: keratocyte-conditioned medium; KDM¹: keratocyte differentiation media which consists of advanced DMEM, ascorbate-2-phosphate (A2-P), and 10 ng/ml fibroblast growth factor-2 (FGF-2); KDM²: keratocyte differentiation media which consists of advanced DMEM, A2-P, 10 ng/ml FGF-2, and 0.1 ng/ml transforming growth factor-β3 (TGF-β3); AM: amniotic membrane; RA: retinoic acid; IGFBP2: insulin-like growth factor binding protein 2.