Pooled Allogeneic MSCs for Ischemia Neovascularization

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current treatments for ischemic conditions such as Critical Limb Ischemia (CLI) and ischemic cardiomyopathy are ineffective for 'no-option' patients, leading to high amputation rates and poor prognosis, with existing revascularization therapies failing due to inappropriate anatomy or frequent re-occlusion.

Innovation Solution

A composition of pooled and expanded allogeneic mesenchymal stromal cells, administered intramuscularly or topically with a conditioned medium containing bioactive factors like VEGF, Ang1, and TGFβ, to induce neovascularization and improve blood flow.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional revascularization therapies (angioplasty and bypass procedures) are used, then blood flow restoration is achieved, but the treatment fails due to inappropriate anatomy or frequent re-occlusion

Engineering Contradiction:

Improvetreatment efficacyVSAvoidanatomical compatibility

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent uses pooled allogeneic mesenchymal stromal cells as an intermediary biological agent to mediate neovascularization. These cells secrete growth factors (VEGF, FGF, PDGF) that stimulate new blood vessel formation, providing a biological bridge that bypasses the limitations of mechanical revascularization methods and adapts to various anatomical configurations.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the fundamental parameter of treatment approach from mechanical/structural (angioplasty, bypass) to biological/regenerative (stem cell therapy). This parameter change allows the treatment to adapt to diverse anatomical situations and reduces re-occlusion by promoting natural vessel formation rather than relying on grafts or stents that can fail.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If pooled allogeneic mesenchymal stromal cells are administered, then neovascularization and blood flow improvement are achieved, but the complexity of cell preparation and administration increases

Engineering Contradiction:

Improvetherapeutic outcomeVSAvoidtreatment protocol complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs pooled allogeneic mesenchymal stromal cells that are prepared in advance from multiple donors, screened, and banked before clinical need arises. This preliminary preparation eliminates the need for time-consuming autologous cell collection and processing at the time of treatment, reducing administrative complexity while maintaining therapeutic efficacy.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The invention merges cells from multiple allogeneic donors into a pooled composition, combining their regenerative capabilities into a single standardized product. This merging approach simplifies the treatment protocol by providing a universal off-the-shelf therapy that eliminates the need for individualized cell processing while delivering consistent therapeutic outcomes.

Inventive Principle:

Principle #5Merging (Combining)

3Reliability

If high dose mesenchymal stromal cells are administered to ensure therapeutic effect, then ischemia management improves, but the cost and logistical requirements increase

Engineering Contradiction:

Improveclinical effectivenessVSAvoidcell dosage requirement

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The mesenchymal stromal cells administered in the patent possess inherent self-proliferative and self-differentiative capabilities. When introduced to the ischemic tissue environment, these cells automatically migrate to affected areas, proliferate locally, and differentiate into endothelial cells and other vascular components, reducing the need for continuous high-dose administrations and optimizing the quantity of cells required for sustained therapeutic effect.

Inventive Principle:

Principle #25Self-service

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The solution significantly reduces rest pain, promotes healing of ulcers and gangrene, increases ankle pressure, and improves quality of life by enhancing neovascularization and angiogenesis, as demonstrated by clinical and preclinical studies.

Implementation Method 1

a conditioned medium derived from pooled allogeneic mesenchymal stromal cells wherein said conditioned medium comprises bioactive factors selected from a group comprising VEGF, Ang1, and TGF β

Methodology Applied

Scientific EffectParacrine signaling:

Implementation Method 2

to induce neovascularization and improve blood flow

Methodology Applied

Scientific EffectAngiogenesis:

Data Source

PatentUS10471101B2Management of ischemia using pooled mesenchymal stromal cell composition

Publication Date: 2019.11.12 STEMPEUTICS RES PRIVATE

AI summary

The present disclosure relates to composition comprising pooled and expanded allogeneic mesenchymal Stromal cells (MSCs) and a method for management of Ischemia using the composition thereof. In particular, the disclosure relates to bone marrow derived pooled and expanded allogeneic MSC compositions with effective dosage ranges and modes/route of administration for effective management of Ischemia. The disclosure also relates to the use of conditioned medium rich in bioactive factors in combination with the cell composition for managing ischemic conditions.