Methods to produce induced pluripotent stem cell-derived mesenchymal stem cells: Mesenchymal stem cells from induced pluripotent stem cells

Table 1 Protocols to produce induced pluripotent stem cell-derived mesenchymal stem cells by the mesenchymal stem cell Switch methods

Ref.	iPSC origin	iPSC to iMSC protocol	Time	Application	Citations
Lian et al[41], 2010	Lung fibroblast	(1) iPSC cultured on a gelatinized dish + KO DMEM + 10% SRM + bFGF + PDGFAB + EGF; and (2) FACS SORTING: CD24- and CD105+ and single cell clones plating	7	Limb ischemia in mice	419
Giuliani et al[42], 2011	Amniocytes	iPSC cultured 4 wk in DMEM/F12 + 10% hiFBS + b-FGF + NEAA + L-Glutamine + β-ME + p/s	28	Immunomodulatory properties of iMSC on NK cytolytic activity	110
Liu et al[43], 2012	Dermal fibroblast	(1) iPSC cultured on collagen-coated dishes with α-MEM + 10% FBS + dexamethasone + magnesium L-ascorbic acid phosphate + p/s; and (2) Cells cultured on collagen-coated dishes with α-MEM + 10% FBS + L-Glutamine + NEAA + p/s	10	iMSC generation w/ Fibrillar Collagen Coating	118
Zou et al[44], 2013	Dermal fibroblasts	iPSC medium switched for MSC medium: DMEM-low glucose + 10% FBS + L-Glutamine	14	Generation of osteogenesis 3D scaffolds	98
Hynes et al[45], 2014	Gingival fibroblast periodontal ligaments	(1) iPSC cultured with MSC medium: α-MEM + FCS + sodium pyruvate + l-ascorbate-2-phosphate + L-Glutamine + NEAA + HEPES + p/s; and (2) Cells cultured on gelatin-coated-flasks then switch to non-coated flasks	14	Generation of iMSC	102
Jeong et al[46], 20141	NA	(1) iPSCs cultured in iMSC-inducing medium: DMEM/F12 + 20% KOSR + SB431542 (TGFβ inhibitor); (2) EB grown on matrigel + DMEM/F12 + 0.5% BSA + 10% ITS + SB431542 (TGFβ inhibitor); and (3) Outgrowth grown with DMEM/F12 + 10% FBS + p/s	17	Duchene muscular dystrophy	17
Hu et al[47], 2015	iPS-S-01, C1P33, PCKDSF001C1	iPSC medium switched for MSC medium: DMEM-low glucose + 10% FBS + L-Glutamine, then cultured in gelatin-coated dishes	14	Limb ischemia	177
Kang et al[48], 2015	Dermal fibroblasts	iPSC cultured with MSC medium: DMEM low glucose + FBS 10% + L-Glutamine + p/s then cultured on gelatin-coated dishes	14	iMSC plasticity (less adipogenesis)	65
Zhang et al[23], 2015	PBMCs	(1) iPSC medium switched for MSC medium: DMEM-low glucose + 10% FBS + L-Glutamine + NEAA + p/s; and (2) Cells cultured on gelatin-coated dishes	17	Cutaneous wound healing	262
Lian et al[49], 2016	NA	(1) iPSC cultured on gelatin-coated plates with MSC differentiation medium: KO DMEM + KOSR + bFGF + PDGFAB + EGF; and (2) FACS: CD24- CD105+ cells cultured on gelatin-coated plates with DMEM + 10% FBS + bFGF + PDGFAB + EGF	20	Directed differentiation of iPSC to MSC	15
Gao et al[50], 2017	Urine cell; Amniocytes	(1) iPSC cultured with MSC-inducing culture media: α-MEM + SRM + sodium pyruvate + l-ascorbate-2-phosphate + L-Glutamine + NEAA + p/s on gelatin-coated plates; and (2) Cells cultured with MSC maintenance medium = high-glucose DMEM + 10% FBS + bFGF + EGF	17	iMSC effect on dendritic cells	27
Nachlas et al[51], 20181	NA	(1) iPSC cultured in suspension (to promote cell aggregate) with differentiation media: KO-DMEM + β-ME+ L-Glutamine + 20% FBS + NEAA + p/s, then, cells were cultured on gelatin coated plates; and (2) Cells cultured with iMSC media: KO-DMEM + L-Glutamine + 10% FBS + NEAA + p/s	12	Generation of valve interstitial-like cells from iMSC	14
Wang et al[52], 2018	Amniocytes	(1) iPSC cultured with induction medium: α-MEM + 10% FBS + p/s + L-Glutamine + NEAA + sodium pyruvate + l-ascorbate-2- phosphate; (2) Cells plated on gelatin-coated plates; and (3) Cells plated on uncoated plates with iPSC-MSC medium = High-Glucose DMEM + FBS + bFGF + EGF + p/s	14	Effect of Dexamethasone on iMSC	3
Wang et al[53], 2018	PBMCs	iPSC cultured with MSC medium: Low-Glucose DMEM + 10% FBS + p/s + L-glutamine	NA	Immunomodulatory properties of MSC, transcriptome analysis	8
McGrath et al[54], 20191	Dermal fibroblast	(1) iPSC-MP thawed and expanded in KO DMEM + bFGF + L-Glutamine + MEM + NEAA + 20% FBS + Antibiotic-Antimycotic + β-ME; and (2) Cell are plated into gelatin coated-plates with KO DMEM + heparin + hPL + bFGF + L-Glutamine + MEM NEAA + Antibiotic-Antimycotic + β-ME	NA	iMSC differentiation: GMP-compatible and xeno-free cultivation	6

iPSC origin refers to the cell type used for reprograming; Time is indicated as the minimum number of days required to obtain iMSCs; Citations show numbers on March 2020.

¹In references indicate the study includes methods in more than one protocol category. bFGF: Basic fibroblast growth factor; β-ME: β-Mercaptoethanol; BSA: Bovine serum albumin; CDM: Chemical defined medium; DMEM/F12: Dulbecco's modified Eagle’s medium F12; EB: Embryoid body; EGF: Epidermal growth factor; FBS: Fetal bovine serum; FCS: Fetal calf serum; HEPES: 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; hiFBS: Heat inactivated fetal bovine serum; hPL: human platelet lysate; IMDM: Iscove's modified Dulbecco's media; iMSCs: Induced pluripotent stem cell-derived mesenchymal stem cells; iPSC: Induced pluripotent stem cell; ITS: Insulin-transferrin-selenium; KO-DMEM: Knockout Dulbecco's modified Eagle's medium; KOSR: Knock-out serum replacement; α-MEM: Minimum essential medium Eagle; NA: Not available; NEAA: Non-essential amino acid; p/s: Penicillin-streptomycin; SRM: Serum replacement medium; TGF: Transforming growth factor.