BDNF-overexpressing human umbilical cord mesenchymal stem cell-derived motor neurons improve motor function and prolong survival in amyotrophic lateral sclerosis mice

ABSTRACT

Objective

To investigate the beneficial effect of brain-derived neurotrophic factor (BDNF) -overexpressing human umbilical cord mesenchymal stem cell (hUC-MSC)-derived motor neurons in the human Cu, Zn-superoxide dismutase1 (hSOD1)^G93A amyotrophic lateral sclerosis (ALS) mice.

Methods

The BDNF gene was transfected into hUC-MSC-derived motor neurons by the lentivirus-mediated method. hSOD1^G93A mice were assigned to the ALS, ALS/MN, and ALS/MN-BDNF groups, and intrathecally administrated phosphate-buffered saline (PBS), motor neurons, or motor neurons overexpressing BDNF, respectively. The control group included non-transgenic wild-type littermates administrated PBS. One month after transplantation, the motor function of the mice was assessed by the rotarod test, and the lumbar enlargements were then isolated to detect the expression of hSOD1 and BDNF by western blotting, and the expression of choline acetyltransferase (ChAT), homeobox protein 9 (HB9), major histocompatibility complex I (MHCI) and microtubule-associated protein-2 (MAP-2) by immunofluorescence assay.

Results

After transplantation, mice in the ALS/MN-BDNF and ALS/MN groups both exhibited longer latency to fall and longer survival than those in the ALS group (P < 0.01 vs. P < 0.05), and the improvement was more significant in the former than in the latter. However, cell transplantation did not delay disease onset. In the lumbar enlargements of the ALS/MN-BDNF and ALS/MN groups, the expression of hSOD1 was slightly reduced without statistical significance (P > 0.05), but the expression of BDNF, ChAT and HB9, and the co-expression of MHCI and MAP-2 were significantly greater than in the ALS group (P < 0.01), with the differences also being more prominent in the former group than in the latter.

Conclusions

Transplantation of BDNF-overexpressing hUC-MSC-derived motor neurons can improve motor performance and prolong the survival of hSOD1^G93A mice. Combining stem cell-derived motor neurons with BDNF might provide a new therapeutic strategy for ALS.

KEYWORDS:

• Amyotrophic lateral sclerosis
• human umbilical cord mesenchymal stem cell
• brain-derived neurotrophic factor
• motor neuron
• hSOD1^G93A mice
• motor function
• survival

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Social Development Project of the Jiangsu Science and Technology Department [BE2015721].

Notes on contributors

Jie Wang

Jie Wang Doctoral candidate of Nanjing Medical University, the Second Affiliated Hospital. Attending Physician of Neurology Department, the Affiliated Jiangning Hospital of Nanjing Medical University.

Weiwei Hu

JWeiwei Hu Residency of Geriatrics Department, Jinling Hospital, Medical School of Nanjing University.

Zehua Feng

Zehua Feng Graduate Student, School of Stomatology, Nanjing Medical University

Meijiang Feng

Meijiang Feng Professor, Chief Physician, Doctoral Supervisor, Engaged in the Research of Neurodegenerative Diseases. Member of Geriatric Branch, Chinese Medical Doctor Association. Member of Geriatric Neurology Group of Geriatric Society, Chinese Medical Association. Vice Chairman of Geriatric Society of Jiangsu Medical Association.