Table 2.

Stem-cell based therapies

Methods	Sub methods	Cells used	End result	In vivo experiment	References
Inner ear stem cell induction	Direct transdifferentiation	SCs	1 HC		Adler et al.,1997 (54); Roberson et al., 2004 (55)
	Mitosis of SCs	SCs, daughter cells	1 SC and 1 HC		Corwin and Contanche, 1988 (50); Ryals and Rubel, 1988 (51)
Cell transplantation	Embryonic stem cells	mESCs	Inner HCLC		Li et al., 2003 (56)
		mESCs	Mechanosensitive inner ear HCLC		Oshima et al., 2010 (57)
		mESCs	SCs, mechanosensitive HCLC, neurons		Koehler et al., 2013 (58)
		mESCs	iHCs with HC specific markers and protrusions reminiscent of stereociliary bundles		Costa et al., 2015 (59)
		hESCs	ONPs, OEPs	Transplanted into adult gerbils;ABR improved	Chen et al., 2012 (60)
		hESCs	iHCs with HC specific markers and protrusions reminiscent of stereociliary bundles		Ronaghi et al., 2014 (61)
		hESCs, hiPSCs	Neurons, SCs, functional HCLCs in 3D culture		Koehler et al., 2017 (62)
	ASCs	BM-MSCs	SGNs	Transplanted into adult gerbils	Matsuoka et al., 2007 (63)
		BM-MSCs	Fibrocyte-like cells	Transplanted into young and adult mice; migrated MSCs seen only in young mice	Kasagi et al., 2013 (64)
		Adult human MSCs	SGNs		Bas et al., 2014(65)
		HUMSCs	Unknown	Transplanted into albino deaf pig; new ABR waves appeared after injection	Ma et al., 2016 (66)
		ratMSCs	HCs	Pre-injected by deferoxamine to home MSCs in noise induced injured cochlea	Peyvandi et al., 2018 (67)
		BM-MSCs	Assess adverse effect	No effect on ABR or DPOAE in rats	Mittal et al., 2019 (68)
		HL-MSCs	Cochlear nerves	Transplanted into intracranial cochlear nerve trunk; ABR improved	Chen et al., 2019 (69)
	Induced pluripotent stem cells	miPSCs	SGNs	Transplanted into mouse cochlea	Nishimura et al., 2009 (70)
		miPSCs	Mechanosensitive inner ear HCLC		Oshima et al., 2010 (57)
		hiPSCs	HCLCs		Ohnishi et al., 2015(71)
		hiPSCs from human MYO15A patients	HCLCs	Corrected mutation by CRISPR/Cas9; functional and morphological rescue	Chen et al., 2016 (72)
		hiPSCs from human MYO7A patients	HCLCs	Same as above	Tang et al., 2016 (73)
		miPSCs	Outer sulcus cell-like cells	Transplanted into mouse otocysts at E11.5	Takeda et al., 2017 (74)
		hiPSCs	OEPs, HCLCs	Transplanted into mouse cochlea; synaptic connection with SGNs	Chen et al., 2018 (75)

SC, Supporting cell; HC, Hair cell; HCLC, Hair cell-like cell; mESC, mouse embryonic stem cell; hESC, human embryonic stem cell; iHC, induced hair cell; ONP, otic neural progenitor; MSC, mesenchymal stem cell; BM-MSC, bone marrow-derived MSC; HL-MSC, human limbus-MSC; HUMSC, human umbilical cord MSC; ABR, auditory brainstem response; DPOAE, distortion product otoacoustic emissions; PSC, pluripotent stem cells; hiPSC, human-induced PSC; miPSC, mouse-induced PSC.