Human umbilical cord derived mesenchymal stem cells in peripheral nerve regeneration

Table 1 Studies of umbilical cord derived mesenchymal stem cells in peripheral nerve axonotmesis and diabetic neuropathy in vivo

Ref.	Study design	Cell source	Subject	Treatment group	Control group	Extraction method	Cell treatment	Delivery method	Follow-up duration (wk)	Results
Hei et al[47], 2016	Case Control	Human	Murine	20 BDNF-transfected UCMSCs; 20 UCMSCs only	20 PBS	Human umbilical vein obtained immediately after delivery	UCMSCs were expanded in keratinocyte-serum free medium with various growth factors. Passage 5 UCMSCs were transfected with adenovirus vector containing BDNF	Xenogenic transplantation into crushed left sciatic nerve	4	Significant improvement in SFI, axon count, axon density, and nerve regeneration in both treated groups. BDNF-loaded UCMSCs showed greater improvements in the above metrics than the UCMSC group
Sung et al[46], 2012	Case Control	Human	Murine	18 UCMSCs	18 PBS	Human umbilical vein obtained immediately after delivery	UCMSCs were culture-expanded in growth factors. Passage 5 UCMSCs were labelled with PKH26 fluorescent cell linker	Xenogenic transplantation into crushed sciatic nerve	4	Significant improvement in SFI, axon density and axon regeneration in UCMSCs group compared to control. Increased BDNF and tyrosine kinase receptor B mRNA compared to control
Gartner et al[48], 2012	Case Control	Human	Murine	6 undifferentiated UCMSCs + PLC; 7 differentiated UCMSCs + PLC; 7 UCMSCs only	6 injury only; 7 injury repaired with PLC only; 6 without injury	UCMSCs from human umbilical cord Wharton’s jelly matrix purchased from third-party source (PromoCell GmbH)	Passage 5 UCMSCs were supplemented with bovine foetal serum. UCMSCs were treated with neurogenic media and differentiated into neuroglial-like cells	Xenogenic transplantation into right sciatic nerve lesion (3 mm) crushed with non-serrated clamp	12	Significant improvement in both undifferentiated and differentiated UCMSCs groups in terms of SFI, EPT, WRL as well as myelin sheath thickness compared to all controls
Gartner et al[49], 2012	Case Control	Human	Murine	6 UCMSCs only; 6 undifferentiated USMSCs + Chitosan type III	6 negative control; 6 wrapped in Chitosan type III	UCMSCs from human umbilical cord Wharton’s jelly matrix purchased from third-party source (PromoCell GmbH)	Passage 5 UCMSCs were loaded on Chitosan type III biomaterial scaffold	Xenogenic transplantation into crushed right sciatic nerve lesion	12	Significant improvement in muscle force deficit and axonal regrowth in UCMSC Chitosan type III group compared to controls
Xia et al[54], 2015	Case Control	Human	Murine	40 UCMSCs	40 saline solution; 40 untreated rats	Human umbilical cord blood plasma obtained from different individuals with identical blood type	UCMSCs were culture-expanded in normal MSC media. Number of passage was not specified	Intravascular injection into left femoral artery of rat with streptozotocin induced diabetic foot ulcer	2	Significant improvement in restoring femoral nerve conduction in UCMSCs group compared to control groups at 3 days, 1 wk and 2 wk

UCMSCs: Umbilical cord derived mesenchymal stem cells; BDNF: Brain-derived neurotrophic factor; SFI: Sciatic function index; PBS: Phosphate buffered saline; PLC: Poly (DL-lactide-ε-caprolactone); WRL: Withdrawal reflex latency; EPT: Extensor postural thrust.