Advances in treatment of neurodegenerative diseases: Perspectives for combination of stem cells with neurotrophic factors

Table 2 Combination therapy of stem cells with neurotrophic factors in Parkinson’s disease

Cell types	Neurotrophic factors	Study design and outcome	Ref.
MSCs	GDNF	MSCs-GDNF transplantation induced a pronounced local trophic effect in the denervated striatum of the 6-OHDA PD rat model.	Moloney et al[62], 2010
MSCs	GDNF	Striatum transplantation of GDNF-releasing Notch-induced BM-MSCs(SB623 cells) significantly decreased amphetamine-induced rotation and promoted DA fiber activation of the 6-OHDA PD rat model.	Glavaski-Joksimovic et al[63], 2010
MSCs	GDNF	The intrastriatal transplantation of BMSCs-GDNF significantly rescued the DA neurons from lactacystin-induced neurotoxicity, with regard to behavioral recovery and striatal dopamine level increase of the lactacystin-lesioned PD rat model, established by intrastriatum transplantation of BMSCs-GDNF followed by lactacystin induction of a lesion at the median forebrain bundles 1 wk later.	Wu et al[64], 2010
MSCs	GDNF	MSCs-GDNF were transplanted into the unilateral striatum and SN of cynomolgus monkeys (PD monkey model) to investigate the protective function of MSCs-GDNF against MPTP-induced injury. Monkeys in the MSCs-GDNF group showed spared contralateral limbs’ motor function and had higher dopamine level and enhanced dopamine uptake in the striatum of the grafted hemisphere.	Ren et al[65], 2013
MSCs	GDNF	The lipopolysaccharide-lesioned PD rat model was used to assess the ability of MSCs-GDNF to protect against lipopolysaccharide-induced neuroinflammation, neurodegeneration, and behavioral impairment. Both experimental groups received a unilateral intrastriatal transplantation of either MSCs-GDNF or MSCs-green fluorescent protein. Protection and/or sprouting of the dopaminergic neuron terminals was induced by the secreted GDNF in the striatum of PD rats.	Hoban et al[66], 2015
MSCs	BDNF	The signals and/or molecules that regulate BDNF expression/delivery were investigated in hMSCs cultures and the effect of epigenetically generated BDNF-secreting hMSCs were evaluated for their impact on intact and lesioned SN. Results showed that the amphetamine-induced motor symptoms were stabilized.	Somoza et al[67], 2010
MSCs	BDNF; GDNF	The intrastriatum transplantation of NTF-SCs posterior to the 6-OHDA lesion led to an obvious amelioration of amphetamine-induced rotations, and the damaged striatal dopaminergic nerve terminal network was regenerated.	Sadan et al[68], 2009
HUVMSCs	NGF	As compared to HUVMSCs-derived dopaminergic-like cells alone, combination with NGF significantly promoted the cell survival, increased the dopaminergic content, and improved motor function of PD rats.	Li et al[69], 2010

6-OHDA: 6-Hydroxydopamine; BDNF: Brain-derived neurotrophic factor; DA: Dopamine; GDNF: Glial cell line-derived neurotrophic factor; hMSCs: Human mesenchymal stem cells; HUVMSCs: Human umbilical vein mesenchymal stem cells; MSCs: Mesenchymal stem cells; NGF: Nerve growth factor; NTF: Neurotrophic factor; NTF-SCs: Neurotrophic factor-secreting stem cells; PD: Parkinson’s disease; SN: Substantia nigra.