期刊
BIOACTIVE MATERIALS
卷 6, 期 8, 页码 2231-2249出版社
KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2021.01.008
关键词
Exosomes; Bone marrow mesenchymal stromal cells; Polypyrrole; Diabetes mellitus; Diabetic peripheral neuropathy
资金
- Department of Biotechnology (DBT) [BT/PR13561/MED/32/392/2016, DBT/IN/SWEDEN/08/AK/2017-1]
- Department of Science and Technology (DST) [DST/NM/NT2018/48, DST/INT/SWD/P-11/2016]
- Ministry of Human Resource Development-IMPRINT [MHRD_6714/Healthcare]
- Ministry of Human Resource Development-SPARC [SPARC/2018-2019/P612/SL]
- Ministry of Human Resource Development-UAY, Govt. of India [MHRD_IITK_006]
- IIT Kanpur
This study developed a treatment approach for diabetic peripheral neuropathy (DPN) using a fused exosomal system combined with electrical stimulation, showing normalization of nerve conduction velocity and compound muscle action potential, muscle recovery, and observed paracrine effects in controlling hyperglycemia and tissue damage attenuation. It provides a promising effective treatment for DPN and contributes to cutting-edge therapeutic approaches.
Diabetic peripheral neuropathy (DPN) is a long-term complication associated with nerve dysfunction and uncontrolled hyperglycemia. In spite of new drug discoveries, development of effective therapy is much needed to cure DPN. Here, we have developed a combinatorial approach to provide biochemical and electrical cues, considered to be important for nerve regeneration. Exosomes derived from bone marrow mesenchymal stromal cells (BMSCs) were fused with polypyrrole nanoparticles (PpyNps) containing liposomes to deliver both the cues in a single delivery vehicle. We developed DPN rat model and injected intramuscularly the fused exosomal system to understand its long-term therapeutic effect. We found that the fused system along with electrical stimulation normalized the nerve conduction velocity (57.60 +/- 0.45 m/s) and compound muscle action potential (16.96 +/- 0.73 mV) similar to healthy control (58.53 +/- 1.10 m/s; 18.19 +/- 1.45 mV). Gastrocnemius muscle morphology, muscle mass, and integrity were recovered after treatment. Interestingly, we also observed paracrine effect of delivered exosomes in controlling hyperglycemia and loss in body weight and also showed attenuation of damage to the tissues such as the pancreas, kidney, and liver. This work provides a promising effective treatment and also contribute cutting edge therapeutic approach for the treatment of DPN.
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