Umbilical Cord as Prospective Source for Mesenchymal Stem Cell-Based Therapy

Table 5

Preclinical studies regarding the use of UC-MSCs.

Model	Animals	Treatment	Results	Cell fate	Reference
Neonatal lung injury	SCID beige mice	1 × 10^6 of human UC-MSCs, i.p.	The restoration of normal lung compliance, elastance, and pressure-volume loops (tissue recoil) associated with alveolar septal widening, suggestive of interstitial matrix modification	Cells tended to remain in the peritoneum or retroperitoneum, although eventually some were disseminated to and were retained in the lungs; differentiation into the relevant cells was not found	[18]
Subtotal liver resection (80% organ weight)	Sprague-Dawley rats	1 × 10^6 of rat UC-MSCs, intrasplenic injection	The stimulation of hepatocyte proliferation and liver weight restoration associated with more rapid recovery of mitochondria number and mitochondrial function of hepatocytes	Cells tended to remain in the spleen, although some part of them migrated to the liver; differentiation into the relevant cells was not studied	[19]
Hindlimb ischemia	BALB/c Slc-nu/nu mice	5 × 10^6 of human UC-MSCs predifferentiated into endothelial lineage, i.m.	The improvement of blood perfusion associated with increased blood vessel density	Some of transplanted cells were found adjacent to vessel walls; differentiation into the relevant cells was not found	[20]
Streptozotocin-induced diabetes mellitus	BALB/c mice	human UC-MSCs predifferentiated into islets like clusters, 10^3 clusters in a immunoisolatory capsule, i.p.	The reduction of hyperglycemia associated with increase of body weight	Cells survived and released insulin for 3 months of follow-up before terminating the experiment	[21]
Full skin excision wound	SCID mice	1 × 10^6 of human UC-MSCs seeded on decellularized amniotic membrane scaffold	The reduction of scar formation with hair growth and improved biomechanical properties of regenerated skin	Cells seeded on decellularized amniotic membrane were grafted onto the area of dermal injury; differentiation into the relevant cells was not studied	[22]
Excisional wound-splinting model	BALB/c nude mice	0,8 × 10^6 of human UC-MSCs, intradermal injection, 0.2 × 10^6 of human UC-MSCs, applied to the wound bed	Accelerated wound healing associated with enhancing collagen deposition and angiogenesis	Engrafted cells did not express CD31 or differentiate into the typical cutaneous resident cells	[23]
Myocardial infarction	C57BL/6 mice	2  ×  10^5 of human UC-MSCs, intramyocardial injection	The preservation of cardiac function associated with increased capillary density and decreased apoptosis in the injured tissue	Cells were not found to engraft the murine heart	[24]
Myocardial infarction	New Zealand white rabbits	5 × 10^6 of human UC-MSCs, subepicardial injection	Improved left ventricular ejection fraction and the percentage of fractional shortening, reduced amount of scar tissue	Some engrafted cells expressed troponin-I, F-actin, and connexin 43	[25]
Myocardial infarction	Guangxi Bama miniswines	40 × 10^6 of human UC-MSCs, intramyocardial injection	Improved myocardial perfusion and function associated with augmented vessel density and reduced cell apoptosis	Part of the engrafted cells differentiated into cardiomyocytes (cTNT+ cells) and vascular endothelia (vWF+ cells) 6 weeks after transplantation	[26]
Radiation myelopathy	Sprague-Dawley rats	1 × 10^6 of human UC-MSCs, i.v., 4 transfusions at 1-week interval	Decreased forelimb paralysis and spinal cord histological damage, increased number of neurons in the anterior horn of the spinal cord, the endothelial cell density and the microvessel density in the white matter and gray matter of the spinal cord; increased relative magnitude of spinal cord blood flow; increased anti-inflammatory cytokine expression in the spinal cord	Cell engraftment and differentiation into the relevant cells were not studied	[27]
Dextran sulfate sodium induced acute colitis	NOD.CB17-Prkdc/J mice	2 × 10^6 of human UC-MSCs, i.v.	The diminution of the severity of colitis and histopathological score associated with decreased myeloperoxidase activity and the expression of cyclooxygenase 2 and iNOS in the colon	Cells were engrafted in the colon; differentiation into the relevant cells was not studied	[28]
Acute carrageenan-induced arthritis and chronic adjuvant induced arthritis models	Wistar rats	1.7 × 10^6 of human UC-MSCs, intraarticular	Faster remission of local and systemic arthritic manifestations associated with immunosuppression via a repression of T-cell proliferation and TGF-β-dependent paracrine promotion of iTreg conversion	Cell engraftment and differentiation into the relevant cells were not studied	[29]
Intracerebral hemorrhage	Sprague-Dawley rats	1 × 10^6 of human UC-MSCs overexpressing HGF, injection into the left ventricle	Motor function recovery associated with nerve fiber remyelination, reduced myelin-associated glycoprotein activity and higher reactivity in myelin basic protein and growth-associated protein-43	Cell engraftment and differentiation into the relevant cells were not studied	[30]
Sinonasal wound healing	New Zealand white rabbits	6 × 10^6 of human UC-MSCs overexpressing HGF, i.v.	Improved nasal wound healing recovery associated with reduced collagen deposition and decreased level of the fibrogenic cytokine TGF-β1	Cells migrated to the injured mucosa and epithelial layer; differentiation into the relevant cells was not found	[31]