Newly Generated 3D Schwann-Like Cell Spheroids From Human Adipose-Derived Stem Cells Using a Modified Protocol

Abstract

Peripheral nerve injury (PNI) is a relatively frequent type of trauma that results in the suffering of many patients worldwide every year. Schwann cells (SCs) are expected to be applied in cell therapy because of their ability to promote peripheral nerve regeneration. However, the lack of clinically renewable sources of SCs hinders the application of SC-based therapies. Adipose-derived stem cells (ADSCs) have generated great interest in recent years because of their multipotency and ease of harvest, and they have already been verified to differentiate into Schwann-like cells (SLCs) in vitro. However, the efficiency of differentiation and the functions of SLCs remain unsatisfactory. We newly generated three-dimensional (3D) SLC spheroids from ADSCs using a modified protocol with human recombinant peptide (RCP) petaloid μ-piece. Morphological analysis, gene expression analysis by qRT-PCR, ELISA measurement of the secretion capabilities of neurotrophic factors, and neurite formation assay were performed to evaluate the functions of these 3D SLCs in vitro. Motor function recovery was measured in a sciatic nerve injury mouse model to analyze the nerve regeneration-promoting effect of 3D SLCs in vivo. The differentiation efficiency and the secretion of neurotrophic factors were enhanced in 3D SLCs compared with conventional SLCs. 3D SLCs could more effectively promote neurite growth and longer neurite extension in a neuron-like SH-SY5Y model. Additionally, 3D SLCs had a better therapeutic effect on nerve regeneration after transplantation into the sciatic nerve injury mouse model. These findings demonstrated that the potential of ADSC-derived SLCs to promote nerve regeneration could be significantly increased using our modified differentiation protocol and by assembling cells into a 3D sphere conformation. Therefore, these cells have great potential and can be used in the clinical treatment of PNI.

Adipose stem cells in tissue regeneration and repair: From bench to bedside

“…Therefore, intravenous injection of ADSCs can also be used to locate and reach the injured nerve site and achieve the same effect as local injection [ 155 ]. However, intravenous injection has the risk of adipose-derived stem cells retaining in other organs and causing damage and teratogenesis [ [156] , [157] , [158] ]. Clinical trials using ADSCs for peripheral nerve regeneration are limited and therefore require further evaluation prior to clinical application.…”

Stemness maintenance of stem cells derived from human exfoliated deciduous teeth (SHED) in 3D spheroid formation through the TGF-β/Smad signaling pathway

“…Cells in suspension can form three-dimensional (3D) spheroids, allowing for significant multiplanar interactions with the cell matrix, which create niches and microenvironments that influence cellular processes such as cell function and fate [30,31]. MSCs cultured in spheroids exhibit a distinctive morphology, characterized by a spherical shape on the inside and an elongated shape on the outside.…”

Sustainable Release of Propranolol Hydrochloride Laden with Biconjugated-Ufasomes Chitosan Hydrogel Attenuates Cisplatin-Induced Sciatic Nerve Damage in In Vitro/In Vivo Evaluation

“…The skull and vertebrae protect the CNS, but not the PNS [ 1 ]. Peripheral nerve injury (PNI) affects more than one million individuals annually, making it a global clinical issue with a substantial socioeconomic cost [ 2 ]. Various factors, including autoimmune illnesses, infections, and trauma, can lead to PNI [ 3 ].…”