Sustained Release of Human Adipose Tissue Stem Cell Secretome from Star‐Shaped Poly(ethylene glycol) Glycosaminoglycan Hydrogels Promotes Motor Improvements after Complete Transection in Spinal Cord Injury Rat Model

Abstract

Adipose tissue‐derived stem cells (ASCs) have been shown to assist regenerative processes after spinal cord injury (SCI) through their secretome, which promotes several regenerative mechanisms, such as inducing axonal growth, reducing inflammation, promoting cell survival, and vascular remodeling, thus ultimately leading to functional recovery. However, while systemic delivery (e.g., i.v. [intravenous]) may cause off‐target effects in different organs, the local administration has low efficiency due to fast clearance by body fluids. Herein, a delivery system for human ASCs secretome based on a hydrogel formed of star‐shaped poly(ethylene glycol) (starPEG) and the glycosaminoglycan heparin (Hep) that is suitable to continuously release pro‐regenerative signaling mediators such as interleukin (IL)‐4, IL‐6, brain‐derived neurotrophic factor, glial‐cell neurotrophic factor, and beta‐nerve growth factor over 10 days, is reported. The released secretome is shown to induce differentiation of human neural progenitor cells and neurite outgrowth in organotypic spinal cord slices. In a complete transection SCI rat model, the secretome‐loaded hydrogel significantly improves motor function by reducing the percentage of ameboid microglia and systemically elevates levels of anti‐inflammatory cytokines. Delivery of ASC‐derived secretome from starPEG‐Hep hydrogels may therefore offer unprecedented options for regenerative therapy of SCI.

Hydrogel scaffolds in the treatment of spinal cord injury: a review

“…In the tissue engineering for the treatment of SCI, the role of hydrogels mainly includes the following points: Firstly, hydrogels provide three-dimensional spatial support for neuronal regeneration and axonal extension, which is conducive to cell growth, proliferation and migration and promotes neural reconstruction ( Chedly et al, 2017 ; Silva et al, 2023 ). Secondly, the hydrogel itself act as a carrier to load stem cells to the site of injury, reducing cell loss to surrounding tissues and off-targeting ( Peng et al, 2023 ).…”

“…By combining hydrogels and cells, it is possible to stabilize the cells at the site of injury while enhancing the effect of hydrogels and better simulating the ECM environment ( Suzuki et al, 2023 ). Compared with adult cells, stem cells have more potential applications, and cells commonly used in central nervous system injury repair cell therapy include NSCs/neural group cells (NPCs), induced pluripotent stem cells (iPSCs), and MSCs ( He et al, 2022 ; Silva et al, 2023 ).…”

Hydrogel and Nanomedicine‐Based Multimodal Therapeutic Strategies for Spinal Cord Injury

“…Polymeric hydrogels have been widely applied in SCI in recent years. [65][66][67] Figure 2 demonstrates the application of polysaccharide hydrogels. Hyaluronic acid (HA) is a common hydrogel polysaccharide.…”

Hydrogel-based treatments for spinal cord injuries

“…Secreted proteome induces neurite growth and cell differentiation. Moreover, hydrogels loaded with secreted proteins effectively improved motor function in rats with SCI [ 110 ].…”