Tissue-Engineered Rostral Migratory Stream for Sustained Neuronal Delivery

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Solution Overview

Problem

Current methods for enhancing neuronal regeneration and migration after brain injury are inefficient, as they fail to provide a sustained influx of new neurons, leading to insufficient functional recovery.

Innovation Solution

A method involving the derivation of astrocytes from gingiva-derived mesenchymal stem cells (GDMSCs) is developed, which are used in a biocompatible construct to promote cell migration and neuronal regeneration, utilizing specific serum-free media compositions and a tissue-engineered rostral migratory stream (TE-RMS) to redirect endogenous neuroblasts into injured regions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional methods are used to enhance neuronal recovery after brain injury, then some neuronal regeneration may occur, but sustained improvements are not achieved due to insufficient influx of new neurons

Engineering Contradiction:
Improveneuronal regeneration rateVSAvoidsustainability of recovery
Core Design Contradiction:
ProductivityVSDuration of action of stationary object

Solution Approach 1:

The patent pre-forms a tissue-engineered rostral migratory stream (teRMS) construct containing neural precursor cells and astrocytes before implantation. This preliminary preparation creates a ready-made migratory pathway that immediately guides new neurons to the injury site, eliminating the delay associated with waiting for natural pathway formation and ensuring sustained neuronal delivery.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The teRMS construct acts as an intermediary structure between the subventricular zone (source of neural precursors) and the brain injury site (destination). This engineered bridge provides a physical and biochemical guide that mediates the migration of neural precursor cells, ensuring they reach the injury site in sufficient numbers for sustained recovery.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Adaptability or versatility

If the brain's natural repair mechanisms are relied upon, then some endogenous neuroblast migration occurs, but the influx of new neurons is insufficient for functional recovery

Engineering Contradiction:
Improvebrain's intrinsic repair capabilityVSAvoidnumber of new neurons
Core Design Contradiction:
Adaptability or versatilityVSQuantity of substance

Solution Approach 1:

The patent pre-populates the teRMS construct with neural precursor cells and astrocytes before implantation. This preliminary action ensures that when the construct is implanted, there is already a sufficient quantity of cells ready to migrate to the injury site, overcoming the limitation of insufficient endogenous neuron production.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent modifies the natural repair process by introducing an engineered construct with controlled cell densities, growth factor concentrations, and structural properties. These parameter changes enhance the quantity of migrating neurons beyond what occurs in natural repair mechanisms alone.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS20240269348A1Tissue-Engineered Rostral Migratory Stream for Neuronal Replacement
Publication Date: 2024.08.15 THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
  • US20240269348A1 patent drawing
  • US20240269348A1 patent drawing
  • US20240269348A1 patent drawing

AI summary

Provided herein is a method of obtaining astrocytes from gingiva-derived mesenchymal stem cells (GDMSC). Also disclosed herein are systems comprising a biocompatible construct and a plurality of astrocytes obtained from a method disclosed herein and methods of making and using the same.