Investigation of neuro-regenerative therapeutic potential of nerve composite matrix hydrogels embedded with adipose-derived stem cells

Matrix Biology Plus, 2024 · DOI: https://doi.org/10.1016/j.mbplus.2024.100165 · Published: November 16, 2024

Simple Explanation

Traumatic spinal cord injury (SCI) leads to permanent loss of motor and sensory function, and current treatments are limited due to the complex injury site. This study explores a new therapy combining human adipose-derived stem cells (hASCs) with nerve composite hydrogels made from decellularized nerve and spinal cord tissue. The researchers tested how different hydrogel compositions affect the secretion of factors that promote blood vessel growth (angiogenesis) and nerve regeneration (neurotrophic effects). They also looked at how well blood vessel cells and nerve cells could grow into these hydrogels. The study found that a hydrogel with a specific ratio of nerve to spinal cord tissue (dSN:dSC = 1:2) showed the most promise for promoting both angiogenesis and nerve regeneration in lab experiments. This suggests it could be a good candidate for further testing in animal models of SCI.

Study Duration

7 and 14 day cultures

Participants

Human adipose-derived stem cells (hASCs), human brain microvascular endothelial cells (HBVECs), and dorsal root ganglia (DRG) from Sprague Dawley rats

Evidence Level

Not specified

Key Findings

1
Hydrogel stiffness was not significantly affected by the ratios of decellularized sciatic nerve (dSN) and spinal cord (dSC) used to create the composite hydrogels.
2
A dSN:dSC ratio of 1:2 in the hydrogel led to increased release of cytokines by the embedded hASCs over time, indicating a more favorable environment for cellular activity.
3
Immediate seeding of human brain microvascular endothelial cells (HBVECs) onto the hydrogels promoted endothelial sprouting, suggesting pro-angiogenic effects.

Research Summary

This study investigates the potential of hASC-embedded nerve composite hydrogels with varying ratios of decellularized sciatic nerve (dSN) and spinal cord (dSC) matrices for SCI repair, focusing on angiogenic and neurotrophic effects in vitro. The mechanical properties, cytokine secretion profiles, and cellular responses of hASCs within different hydrogel compositions were analyzed. The findings suggest that the dSN:dSC = 1:2 hydrogel exhibits superior therapeutic potential, warranting further in vivo studies. Proteomic analysis revealed differences in ECM composition between dSN and dSC, potentially influencing hASC behavior and therapeutic efficacy. The study provides insights into optimizing hydrogel composition for SCI treatment.

Practical Implications

Optimized Hydrogel Composition

The findings support the development of nerve composite hydrogels with a dSN:dSC ratio of 1:2 as a promising therapeutic approach for SCI.

Targeted ECM Modification

The study highlights the potential for targeting specific ECM proteins within hydrogels to improve their therapeutic efficacy for SCI.

Combinatorial Therapy

Combining hASCs with nerve composite hydrogels represents a promising combinatorial therapy approach for SCI repair, enhancing both angiogenesis and neurotrophic effects.

Study Limitations

1
The molecular mechanisms underlying the interactions between different ECM compositions and encapsulated hASCs need further investigation.
2
Batch-to-batch inconsistency of decellularized tissues is a potential challenge, which can be mitigated by controlled utilization of animals.
3
Further investigation should include directionality of neurite outgrowth to improve the accuracy and efficiency of regenerating axons at the injury site.

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