Table 3.

Systemic administration of mesenchymal stem/stromal cells for luminal inflammatory bowel disease. 5-ASA, 5-aminosalicylic acid. Allo-BM-MSCs, allogeneic bone marrow mesenchymal stem/stromal cells. AZA, azathioprine. CD, Crohn’s disease. CDAI, Crohn’s Disease Activity Index. HBI, Harvey-Bradshaw Index. SAEs, serious adverse events. UC, ulcerative colitis. Um-MSCs, umbilical cord mesenchymal stem/stromal cells.

Study	Study Type	N	Intervention	Primary Outcomes	Results	Comments
Melmed et al. [53]	Phase Ib/IIa	50 luminal CD	Phase Ib: two infusions of 8U PDA-001 (1.5 × 109 cells) one week apart. Phase IIa: two infusions of placebo, 1U PDA-001 (1.5 × 108 cells), or 4U PDA-001 (6 × 108 cells) one week apart.	Decrease in CDAI by ≥100 points and/or 25% from baseline at weeks 4 and 6.	Phase Ib: primary efficacy not reported Phase IIb: Placebo: 0/16 1U PDA-001: 5/15 (33%) 4U PDA-001: 5/13 (38.5%)	NCT01155362 PDA-001 is comprised of allogeneic placental MSCs. Study was suspended early due to several SAEs.
Dhere et al. [49]	Phase I	12 luminal CD	Single infusion of 2, 5, or 10 × 106 auto-BM-MSCs/kg.	Decrease in CDAI by ≥ 100 points at 2 weeks.	5/11 (45.4%) achieved clinical response.	NCT01659762
Hu et al. [54]	Phase I/II	70 with UC	Group I: IV injection of 0.5 × 106 Um-MSCs/kg, followed by intra-arterial injection of 1.5 × 107 MSCs one week later. Group II: placebo (normal saline) in same manner as group I.	Decrease in total Mayo UC activity score of ≥3 and ≥30% from baseline, with accompanying decrease in rectal bleeding subscore of ≥1 point or absolute subscore for rectal bleeding of 0 or 1.	29/34 (85.3%) with clinical response in group I vs. 6/36 (16.7%) at 3 months.	NCT01221428
Knyazev et al. [50]	Phase I	22 with UC	Control: 5-ASA and steroid taper. Treatment: 1.5–2 × 106 allo-BM-MSCs/kg at weeks 0, 1, and 26, in addition to 5-ASA and steroid taper.	Remission rate and average remission duration.	Remission rate of 50% (6/12) in treatment group vs. 10% (1/10) in control group at 3 years. Remission duration of 22 months in treatment group vs. 20 months in control group at 3 years.
Gregoire et al. [52]	Phase I/II	13 luminal CD	2 injections of 1.5–2.0 × 106 allo-BM-MSCs /kg 4 weeks apart.	Decrease in CDAI by ≥100 points at 8 weeks.	2/13 (15.4%) with clinical response at 8 weeks.	NCT01540292
Zhang et al. [55]	Phase I	82 luminal CD	Control: “background treatment.” Treatment: infusion of 1 × 106 Um-MSCs/kg once a week for 4 weeks.	Decrease in CDAI, HBI, and corticosteroid usage.	CDAI decreased by 62.5 in Um-MSC vs. 23.6 in control at 12 months. HBI decreased by 3.4 in Um-MSC vs. 1.2 in control at 12 months. Corticosteroid dosage decreased by 4.2 mg/day in Um-MSC vs. 1.2 mg/day in control at 12 months.	NCT02445547
Knyazev et al. [51]	Phase I/II	34 luminal CD	Group 1: 2 × 106 allo-BM-MSCs/kg at months 0, 1, and 6, with AZA 2–2.5 mg/kg. Group 2: 2 × 106 allo-BM-MSCs/kg at months 0, 1, and 6.	Clinical remission (CDAI < 150) at 12 months.	At 12 months, average CDAI was 99.9 in group 1, 100.6 in group 2.