Table 2.

Randomized Controlled Trial Studies Studying Unselected BM-MNC or PB-MNC for Critical Limb Ischemia

Reference (Trial)	Cell Type	Cell Dose	Delivery Method	Subject No.	Indication	Follow-Up	Outcome
Bone marrow–derived mononuclear cells
Van Tongeren et al98	BM-MNC	109 cells (included 106 CD34+ cells)	IA+IM 15:IM 12:IA+IM	27	No option CLI	12 mo	Significant improvements for both tx arms in ABI, pain score, pain-free walking distance with cell therapy compared with baseline. No significant difference in limb salvage rates between tx arms
Walter et al163 (PROVASA)	BM-MNC	108 cells (included 106 CD34+) Dose escalation: single dose or double dose	IA	40	CLI RC 4–6	6 mo	Significant improvements in ulcer healing, rest pain with cell therapy in this multicenter, double-blind, randomized-start clinical trial. No significant improvements found in ABI or limb salvage
Iafrati et al88 (BMAC)	BM-MNC	109 cells	IM	48	RC 4–5	3 mo	Improvement in amputation, pain, quality of life, Rutherford classification, and ABI compared with control
Benoit et al87 (BMAC)	BM-MNC	109 cells	IM	48	RC 4–5	6 mo	Lower amputation rates compared with placebo
Prochazka et al89	BM-MNC	Unspecified	IM	96	RC 4–6	4 mo	Significant improvements in limb salvage rates and ABI
Peripheral blood–derived mononuclear cells
Huang et al90	PB-MNC	108 (≈0.4% CD34+) cells	IM	28	RC 4–6	3 mo	Significant improvements in ABI, ulcer healing, Laser Doppler blood perfusion, angiographic scores, limb salvage with cell therapy compared with randomized control
Ozturk et al94	PB-MNC	107	IM	40	RC 4–6	3 mo	Improved ABIs, pain scores
Mohammadzadeh et al93	PB-MNC	107	IM	21	CLI, DM	3 mo	Improved ABIs, amputation rates

ABI indicates ankle brachial index; BM-MNC, bone marrow–derived mononuclear cell; CLI, critical limb ischemia; DM, diabetes mellitus; IA, intra-arterial; IM, intramuscular; PB-MNC, peripheral blood–derived mononuclear cell; and RC, Rutherford classification.