Mesenchymal stem cells in chemotherapy‐induced peripheral neuropathy: A new challenging approach that requires further investigations

Abstract

Chemotherapeutic drugs may disrupt the nervous system and cause chemotherapyinduced peripheral neuropathy (CIPN) as side effects. There are no completely successful medications for the prevention or treatment of CIPN. Many drugs such as tricyclic antidepressants and anticonvulsants have been used for symptomatic treatment of CIPN. Unfortunately, these drugs often give only partial relief or have dose-limiting side effects. Thus, the treatment of CIPN becomes a challenge because of failure to regenerate and repair the injured neurons. Mesenchymal stem cell (MSC) therapy is a new attractive approach for CIPN. Evidence has demonstrated that MSCs play important roles in reducing oxidative stress, neuroinflammation, and apoptosis, as well as mediating axon regeneration after nerve damage in several experimental studies and some clinical trials. We will briefly review the pathogenesis of CIPN, traditional therapies used and their drawbacks as well as therapeutic effects of MSCs, their related mechanisms, future challenges for their clinical application, and the additional benefit of their combination with pharmacological agents. MSCs-based therapies may provide a new therapeutic strategy for patients suffering from CIPN where further investigations are required for studying their exact mechanisms. Combined therapy with pharmacological agents can provide another promising option for enhancing MSC therapy success while limiting its adverse effects.

IFN-γ-Primed hUCMSCs Significantly Reduced Inflammation via the Foxp3/ROR-γt/STAT3 Signaling Pathway in an Animal Model of Multiple Sclerosis

“…Studies have shown that MSCs may suppress the activity of B cells and reduce autoantibody production ( 18 ). In addition, they can promote the expansion of Tregs by secreting IL-10, IDO, and transforming growth factor beta (TGF-β) ( 19 , 20 ). Moreover, MSCs can suppress the differentiation and proliferation of Th cells and increase the suppressive proportion of B cells via IDO ( 21 , 22 ), and IFN-γ is the main inducer of IDO ( 23 ).…”

Chemotherapy-induced peripheral neuropathy—part 2: focus on the prevention of oxaliplatin-induced neurotoxicity

“…Hence, MSC-based therapies may provide a new therapeutic strategy for patients suffering from CIPN. Combined therapy using 'traditional' pharmacological agents and MSCs might also be an interesting approach for CIPN prevention and treatment [157].…”

Targeting strategies for oxaliplatin-induced peripheral neuropathy: clinical syndrome, molecular basis, and drug development

“…The dual phosphodiesterase 4B/7A inhibitors and TRPA1 channel antagonists (HC-030031) reduced tactile allodynia in an OIPN model with TNFα-lowering effect [ 168 ]. Combined therapy using “traditional” pharmacological agents and mesenchymal stem cells (MSCs) may also be important in the prevention and treatment of CIPN [ 203 ]. Based on the double action of OHP dosage in neuropathy and chemotherapeutic effect, some chemosensitizers such as cerulenin may enhance the therapeutic effects of OHP, and thus lower the OHP-induced neuropathy [ 204 ]; however, individual precision treatment strategies warrant further exploration [ 205 ].…”