Immunomodulatory Role of Mesenchymal Stem Cell Therapy in Vascularized Composite Allotransplantation

Table 1

Preclinical in vivo studies assessing the immunomodulatory effect of MSC therapy in vascularized composite or skin allotransplantation.

Authors	Animal (number)	Allogeneic transplant	MSC type	MSC dose; (days of infusion)	Other treatments; (days of administration)	Days of therapy-free follow-up	Increased graft survival in MSC alone? ( value)	Percent of grafts surviving until end point
Bartholomew et al. (2002) [23]	Baboon (8)	Skin	BMSC; allogeneic	20 × 10^6 cells/kg (0, 3)	None		Yes (unstated)
Aksu et al. (2008) [24]	Rat (44)	Skin	BMSC; allogeneic	2-3 × 10^6 cells (0, 7, 14, 21)	TBI (1), CsA (0–20),; BM IV (0, 7, 14, 28)
Sbano et al. (2008) [25]	Rat (62)	Skin	BMSC; allogeneic	5.7 × 10^6 cells/kg (0); 10.3 × 10^6 cells/kg (0)	CsA (0–30)		No (<0.001)
Pan et al. (2010) [26]	Rat (47)	Hind-limb	BMSC; allogeneic	200 × 10^6 cells (−30)	TBI (−30), RAPA (−30–100), ALG (−6, −4, −2), BMT (−30)	0^†	Yes (unstated)	100
Kuo et al. (2009) [27]	Swine (23)	Hind-limb	BMSC; allogeneic	1 × 10^7 cells (−1, 3, 7, 14, 21)	TBI (−1), CsA (0–28)	280	Yes (0.02)	60
Kuo et al. (2011) [28]	Swine (16)	Hind-limb	BMSC; allogeneic	1 × 10^7 cells (−1, 1, 3, 7, 14, 21)	TBI (−1), CsA (0–28)	100	Yes (0.018)	67
Kuo et al. (2011) [29]	Rat (28–36)	Hind-limb	ASC; allogeneic	2 × 10^6 cells (7, 14, 21)	ALS (−4, 1), CsA (0–28)	180		89
Kuo et al. (2012) [30]	Swine (16)	Facial	BMSC; allogeneic	2.5 × 10^7 cells (−1, 1, 3, 7, 14, 21)	CsA (0–28)	67^††	Yes (0.123)	0
Larocca et al. (2013) [31]	Mouse (21)	Skin	ASC; allogeneic	5 × 10^5 cells (1)	BM IV		Yes^§ (<0.05)
Lee et al. (2014) [32]	Mouse (48)	Skin	ASC or CM; human	1 × 10^6 cells or 0.3 mL CM (0)	None		Yes^§§ (<0.005)
Jeong et al. (2014) [33]	Rat (21)	Hind-limb	BMSC; allogeneic	1 × 10^5 cells (0, 1, 2, 3)	None		Yes (<0.001)
Cheng et al. (2014) [34]	Rat (32)	Hind-limb	ASC; syngeneic	2 × 10^6 cells (1)	TBI (−1), ALG (−1, 10), CsA (0–10)	140		67
Ramirez et al. (2014) [35]	Rat (47)	Hind-limb and/or HAW	ASC; syngeneic	2 × 10^6 cells (1, 8, 15)	ALS (−1, 10), CsA (0–10)	140		38 HLOMC,; 0 HAW,; 0 HLOMC + HAW
Plock et al. (2015) [36]	Rat (35)	Hind-limb	BMSC or ASC; allogeneic	1 × 10^6 or 5 × 10^6 cells (1)	ALS (−4, 1), tacrolimus (0–20)	100		46 BMSC,; 47 ASC
Davis et al. (2014) [37]	Mouse (38)	Skin	BMSC or ASC; human	5 × 10^5, 3 × 10^6 cells, respectively (7)	Anti-CD4/CD8 mAbs (0, 2, 5, 7, 14), busulfan (5)		Yes (unstated)
Hivelin et al. (2016) [38]	Rat (24)	Hemifacial	BM, BMSC,; D/RCC	100 × 10^6, 5 × 10^6, 10 × 10^6 cells, respectively; intraosseous injections	Anti-αβ-TCR mAb, CsA (1–7)	Control: 25–29^††,; BMSC: 27–32^††	Yes (0.03)	0

↑: increased; ALG: antilymphocyte globulin; ALS: antilymphocyte serum; ASCs: adipose tissue-derived mesenchymal stem cells; BM: bone marrow; BMSC: bone marrow-derived mesenchymal stem cell; BMT: bone marrow transplant; CM: conditioned media; CsA: cyclosporine A; D/RCC: donor-recipient chimeric cells; HAW: hemiabdominal wall; mAbs: monoclonal antibodies; MSC: mesenchymal stem cell; RAPA: rapamycin; TBI: total body irradiation; HLOMC: hind-limb osteomyocutaneous combined flap. CM from equal number of cells and concentrated 25-fold; 100-day follow-up on CsA monotherapy; when final surviving graft perished; only for donor-specific ASC; for both cells and CM.