De-Differentiated Fibroblast Exosomes for Disc Regeneration
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Solution Overview
Problem
Intervertebral discs degenerate due to aging, mechanical stress, and genetic changes, leading to structural integrity loss, decreased hydration, and apoptosis of nucleus pulposus cells, which current treatments like gene therapy and stem cell therapy have not adequately addressed.
Innovation Solution
Utilizing conditioned media from de-differentiated fibroblasts, particularly exosomes expressing markers such as CD63, CD9, MHC I, and CD56, to regenerate injured discs and inhibit nucleus pulposus cell apoptosis, potentially through exposure to hypoxia and histone deacetylase inhibitors like valproic acid.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments like gene therapy and stem cell therapy are used, then some therapeutic effect is achieved, but they have not adequately addressed disc degeneration and nucleus pulposus cell apoptosis
Solution Approach 1:
The patent uses conditioned media from de-differentiated fibroblasts as a surrogate system that copies and transfers beneficial cellular properties to treat disc degeneration. The fibroblasts are de-differentiated to resemble nucleus pulposus cells, and their conditioned media contains factors that can inhibit apoptosis and promote regeneration without requiring direct transplantation of stem cells or genetic modification
Solution Approach 2:
The patent changes the differentiation state parameter of fibroblasts by exposing them to hypoxia and histone deacetylase inhibitors, transforming them from a differentiated state to a de-differentiated state that resembles nucleus pulposus cells. This parameter change enables the fibroblasts to produce conditioned media with regenerative properties
2Reliability
If de-differentiated fibroblasts are used to produce conditioned media, then disc regeneration and apoptosis inhibition are achieved, but the process requires complex culture conditions including hypoxia and histone deacetylase inhibitors
Solution Approach 1:
The patent performs preliminary de-differentiation of fibroblasts under controlled hypoxia and histone deacetylase inhibitor exposure before collecting the conditioned media. This preliminary action transforms the cells into a regenerative state, and the resulting conditioned media can then be applied therapeutically without requiring the complex culture conditions to be maintained during treatment
Solution Approach 2:
The patent extracts the beneficial regenerative factors from the de-differentiated fibroblasts by collecting their conditioned media. This separates the therapeutic agents from the complex cellular system, allowing the media to be applied therapeutically without requiring the presence of live cells or maintenance of complex culture conditions
Data Source
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AI summary
Embodiments of the disclosure include methods and compositions for disc repair in a mammal using conditioned media (and/or one or more components therefrom) from fibroblasts that have been de-differentiated and cultured optionally with one or more particular conditions and/or compositions. In specific cases, fibroblasts that have been de-differentiated are exposed to hypoxia, histone deacetylase inhibitor(s), DNA methyltransferase inhibitor(s), or a combination thereof, and the conditioned media therefrom is provided in an effective amount to an individual.