Insight in Hypoxia-Mimetic Agents as Potential Tools for Mesenchymal Stem Cell Priming in Regenerative Medicine

Table 6

Effect of hypoxia on MSC engraftment, migration, and secretion profile.

Treatment conditions		Stem cell type	The effect compared to normoxia (methods of analysis)	Ref.
O2 concentration	Time/passage
1%	1 d	hBM-MSC	CX3CR1and CXCR4 upregulated (qRT-PCR)	[172]
1%	2 d	hBM-MSC	VEGF secretion in spheroids increased (ELISA) on a rat model, collagen deposition (Masson’s trichrome stain) enhanced, vascularization and bone formation promoted (high-resolution radiographs), and healing after transplantation of primed MSC spheroids improved compared to transplantation of individual cells	[89]
1%	2 d	hBM-MSC	VEGF and NANOG upregulated (qRT-PCR)	[57]
1%	2 d; 2 d	rBM-MSC	VEGF upregulated (RT-PCR), VEGF increased (WB, ELISA)	[80]
1%	>2 d	mBM-MSC	Cxcr4 downregulated (qRT-PCR)	[143]
1%	10 d	hBM-MSC	VEGF and NANOG upregulated (qRT-PCR)	[57]
1%	14 d	mBM-MSC	On a myocardium infarction (MI) mouse model, cardiomyocyte survival reduced due to MCT-4 (WB) increase, and fibrosis in cardiac tissue initiated	[68]
1-3%	16 h	hBM-MSC	Migration potential increased (scratch test)	[81]
2%	Up to 7 passages	hBM-MSC	ECM secretion enhanced (fibronectin and collagen type II fluorescent staining, CLSM), expression of connexin-43 increased (fluorescent staining, CLSM)	[38]
2.5%	>3 d	hUCB-MSC	Migration potential increased	[60]
5%	>8 h	mBM-MSC	CXCR4, MMP 9, and 14 increased (WB), after MI treatment on the rat model the left ventricular (LV) fibrosis reduced, improved LV function	[152]
5%	4 d	hBM-MSC	VEGF increased (ELISA)	[65]
5%	10 d	hBM-MSC	MMP7-16 and TIMP1-3 upregulated (qRT-PCR)	[65]

Hypoxic pretreatment 4-48 hours at 1% O₂ and then reoxidation 8 hours at 21% O₂; hypoxic preconditioning in 2.5% O₂ for 15 minutes, then reoxygenation at 21% O₂ for 30 minutes, and again hypoxia preconditioning at 2.5% O₂ for 3 days; hypoxic pretreatment 8 hours at 5% O₂ and then 30 minutes of reoxidation at 21% O₂; h: human; m: mouse; r: rat.