Induced pluripotent stem cells: Mechanisms, achievements and perspectives in farm animals

Table 1 Most advanced achievements in induced pluripotent stem cells from domestic animals

Domestic species	Cell type	Transduction	Reprogramming factors	Culture medium	Differentiation		Chimera	Germline contribution	Ref.
					In vitro	In vivo
Buffalo	Fetal fibroblasts	Retrovirus	OSKM	A	EBs	Teratoma	NA	NA	[13]
Cattle	Fetal fibroblasts	Retrovirus	OSKM, OSKMLN, OSKM	B	EBs	Teratoma	NA	NA	[9]
	Fetal fibroblasts	Plasmid	OSKM	C	EBs	Teratoma	NA	NA	[53]
Dog	Skin fibroblasts	Lentivirus	Human OKSM	J	EBs	Teratoma	NA	NA	[56]
	Skin fibroblasts	Retrovirus	Mouse OKSM	K	EBs	Teratoma	NA	NA	[54]
Goat	Fibroblasts	Inducible lentivirus	OSKM, SV40 large T and hTERT	A	EBs	Teratoma	NA	NA	[12]
Horse	Fetal fibroblasts	PiggyBac transposon	OSKM	E	EBs	Teratoma	NA	NA	[10]
	Adult fibroblasts	Retrovirus	OSK	F	EBs	Teratoma	NA	NA	[61]
Pig	Mesenchymal stem cells from bone marrow	Lentivirus	OSNKLM	G	EBs	NA	Low grade	Two offspring	[26]
	Fetal fibroblasts	Sleeping Beauty transposon	Mouse OSKM	I	Neuronal lineage	Teratoma	NA	NA	[91]
Rabbit	Skin fibroblasts	Retrovirus	Human OKSM	I	EBs	Teratoma	NA	NA	[72]
Sheep	Fetal fibroblasts	Retrovirus	MKOS	D	EBs	Teratoma	Low grade	NA	[25]

A: DMEM, ESC FBS, L-glutamine, NEAA, β-Me, bFGF, LIF and MEFs; B: DMEM, KSR, L-glutamine, NEAA, β-Me, bFGF and MEFs; C: DMEM/F12 + N2 and Neurobasal with B27, L-glutamine, hLIF, PD0325901, CHIR99021 and MEFs; D: KO-DMEM, SR, L-glutamine, NEAA, 2-Me, human bFGF and MEFs; E: DMEM, FBS, L-Glutamine, NEAA, β-Me, Sodium Pyruvate, LIF, bFGF, Doxycycline, CHIR99021, PD0325901, A83-01, Thiazovivin, B431542 and 1:1 MEFs and EFFs; F: α-MEM, FBS, deoxyribonucleosides, ribonucleoside, glutamax, NEAA, β-Me, ITS, human LIF, βFGF, EGF and MEFs; G: DMEM/F12, KSR, L-glutamine, NEAA, β-Me, FGF and MEFs; H: KO DMEM, KSR, glutamax-L, NEAA, 2-Me, pLIF, forskolin and collagen I; I: DMEM/F12, KSR, L-glutamine, NEAA, β-Me, bFGF and MEFs or gelatinized plates; J: KO DMEM, ESC FBS, bFGF, hLIF and MEFs; K: DMEM/F12, KSR, bFGF, hLIF, PD0325901, CHIR99021 and MEFs. DMEM: Dulbecco’s modified Eagle´s medium; LIF: Leukemia inhibitory factor; IGF1: Insulin-like growth factor 1; NEAA: Nonessential amino acids; FBS: Fetal bovine serum; KO: Knockout; MEM: Minimum essential medium; ITS: Insulin-transferring selenium; bFGF: Basic fibroblastic growth factor; DOX: Doxycycline; EB: Embryonic body; FCS: Fetal calf serum; hSCF: Human stem cell factor; KSR: Knockout serum replacement; MEFs: Mouse embryonic fibroblasts; OKSM: Oct-4, Klf4, Sox2, and c-Myc; OKSMLN: Oct-4, Klf4, Sox2, c-Myc, Lin28 and Nanog; VPA: Valproic acid; Me: Mercaptoethanol.

Table 2 Achievements with induced pluripotent stem cells from rodents, farm animals and humans

	Rodents	Farm animals	Human
iPS cells	√√	√√	√√
In vivo differentiation	√√	√√	√√
In vitro differentiation	√√	√√	√√
Chimera	√√	√/-	Ethically not allowed
Germline transmission	√√	√/-	Ethically not allowed
Follow up generations	√√	--	Ethically not allowed
Transplantation of iPS cell-derived cells	√√	√/-	No clinical studies to date1

√√: Fully proven; √/-: Partially proven; --: Not achieved yet;

¹The first clinical study was recently initiated (http://www.riken.jp/en/pr/press/2013/20130730_1). iPS: Induced pluripotent stem.