Mesenchymal Stromal Cell Therapy for Pancreatitis: A Systematic Review

Table 1

Summary of studies addressed MSCs in acute pancreatitis. L-arg: L-arginine; Na TCA: sodium taurocholate solution; TCA: taurocholic acid solution; LPS: lipopolysaccharide; rBM-MSCs: rat bone marrow mesenchymal stromal cells; hBM-MSCs: human bone marrow mesenchymal stromal cells; UCMSCs: umbilical cord mesenchymal stromal cells; hUCMSCs: human umbilical cord mesenchymal stromal cells; rFMMSCs: rat fetal membrane mesenchymal stromal cells; SD rats: Sprague Dawley rats; mir-9: microRNA-9; N/A: not applicable; PBS: phosphate buffer saline.

Author	Pancreatitis induction method	Source of MSCs	Dose of MSCs	Route of MSC infusion	Timeline of MSC therapy		Specific treatment of MSCs	Outcome
					Treatment time point	Scarification timeline		Serum amylase and lipase	Histological feature of pancreas	Mechanism of action of infused MSCs
Qu et al., [53]	L-arg	rBM-MSCs	1 ml cell suspension: 1 × 10^7 cells/ml	Tail vein of SD rats	4 days	After 7, 14, and 21 days	N/A	Decreased	Decreased	(i) Pancreatic lineage differentiation
Qian et al., [54]	Na TCA and Caerulein	rBM-MSCs	1 × 10^7cells/kg	Tail vein of SD rats	24 hrs.	After 3 days	miR-9 modified BM-MSCs	Decreased	Decreased	(i) Immunomodulatory effect; (ii) Antiapoptotic effect; (iii) Antioxidant effect; (iv) Enhancement of regeneration of damaged pancreas; (v) Deliver miR-9 to the injured pancreas or peripheral blood mononuclear cell (PBMC), which can target the NF-κB1/p50 gene and inhibit the NF-κB signaling pathway
He et al., [47]	Na TCA	hBM-MSCs	2.0 × 10^6 cells	Tail vein of C57BL/6 mice	6 hrs.	N/A	hBM-MSCs transfected with TSG-6 siRNA	Decreased	Decreased	(i) Immunomodulatory effect
Jung et al., [45]	Cerulein and sequential LPS	hBM-MSCs	1 × 10^6 cells	Tail vein of SD rats	24 hrs	After 3 days	N/A	Decreased	Decreased	(i) Immunomodulatory effect; (ii) Antioxidant effect
Yin et al., [48]	L-arg	rBM-MSCs	1 × 10^6 cells	Tail vein of SD rats	3 hrs.	After 1, 2, and 3 days	N/A	Decreased	Decreased	(i) Immunomodulatory effect
Qian et al., [46]	Na TCA	rBM-MSCs	1 × 10^7 cells/ml/kg	Tail vein of SD rats	1, 5, 7, and 10 days	N/A	BM-MSCs pretreated with SDF-1α	Decreased	Decreased	(i) Immunomodulatory effect; (ii) Angiogenesis-enhancing effect
Tu et al., [52]	Na TCA	rBM-MSCs	2 × 10^6 cells/ml	Dorsal penile vein of SD rats	1 hr.	After 6, 12, 24, and 48 hrs.	N/A	Decreased	Decreased	N/A
Chen et al., [50]	Na TCA	BM-MSCs (source not specified)	1 × 10^6 cells	Tail vein of SD rats	0 hr.	After 6 hrs.	N/A	Decreased	Decreased	N/A
					0, 6 hrs.	After 12 hrs.
					0, 6, and 12 hrs.	After 24 hrs.
Tu et al., [51]	Deoxy-STC	rBM-MSCs	2 ml cell suspension: 1 × 10^6 cells/ml	Tail vein of SD rats	N/A	After 6, 24, and 72 hrs.	N/A	Decreased	Decreased	(i) Immunomodulatory effect; (ii) Antioxidant effect
Zhao et al., [49]	TCA	rBM-MSCs	5–7 × 10^7 cells	Tail vein of SD rats	24 hrs.	After 72 hrs.	N/A	Decreased	Decreased	(i) Immunomodulatory effect
Jung et al., [44]	Mild acute pancreatitis: cerulein; Severe acute pancreatitis: Na TCA	hBM-MSCs	N/A	Tail vein of SD rats	N/A	After 3 days	N/A	Decreased	Decreased	(i) Immunomodulatory effect; (ii) Antiapoptotic effect (apoptosis of acinar cells was reduced in severe acute pancreatitis than in mild acute pancreatitis)
Hua et al., [57]	Na TCA	hUCMSCs	1 × 10^6 cells in 200 μl saline	Tail vein of SD rats	12 hrs	After 3 days	ANGPT1-transfected hUCMSCs	Decreased	Decreased	(i) Immunomodulatory effect; (ii) Angiogenesis-enhancing effect
Yang et al., [56]	Na TCA	hUCMSCs	5 × 10^6 cells/kg	Tail vein of SD rats	0, 1, 6, and 12 hrs	After 48 hrs.	N/A	Decreased	Decreased	(i) Immunomodulatory effect
			5 × 10^4, 5 × 10^6, and 1 × 10^7 cells/kg		1 hr
			5 × 10^6		6 hrs
Meng et al., [55]	Na TCA	hUSMSCs	1 × 10^7 cells/kg	Tail vein of SD rats	12 hrs	After 1, 3, and 5 days	N/A	Decreased	Decreased	(i) Antiapoptotic effect (reduce acinar cell apoptosis); (ii) Immunomodulatory effect
Kim et al., [43]	Na TCA	Canine adipose tissue-derived MSCs	2 × 10^6 cells/kg in 200 μl PBS	Tail vein of SD rats	N/A	After 3 days	N/A	Decreased	Decreased	(i) Immunomodulatory effect
K et al., 2016	TCA	rFMMSCs	1 × 10^6 cells in 200 ul PBS	Penile vein of August Copenhagen Irish rats	N/A	After 4 days	N/A	Decreased	Decreased	(i) Immunomodulatory effect