NK1R+ Mesenchymal Stem Cell Isolation for Cardiac Repair

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Solution Overview

Problem

Current treatments for cardiovascular diseases, such as ischemic cardiomyopathy, lack effective therapies to improve cardiac function and reduce scar size after myocardial infarction, with existing stem cell therapies requiring lengthy culture times to obtain sufficient quantities.

Innovation Solution

Isolation and administration of NK1R+ mesenchymal stem cell precursors from bone marrow, which can be mobilized by endogenous signals of pain, allowing for immediate therapeutic use and potential to regenerate myocardium and repair damaged cardiac tissue.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If unselected mesenchymal stem cells are used for therapy, then sufficient cell quantities can be obtained, but the therapeutic efficacy is limited and culture time is lengthy

Engineering Contradiction:
Improvecell quantityVSAvoidtherapeutic efficacy
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The patent extracts and isolates a specific subset of mesenchymal stem cells expressing the NK1R marker from the general mesenchymal stem cell population. This selective extraction of NK1R+ cells provides both sufficient cell quantities for therapy and enhanced therapeutic efficacy, resolving the contradiction between quantity and productivity by focusing on a high-potency cell subset rather than using unselected cells.

Inventive Principle:
Principle #2Taking out (Extraction)

2Quantity of substance

If stem cells are cultured to obtain sufficient quantities, then enough cells are available for therapy, but the culture time is lengthy and delays treatment

Engineering Contradiction:
Improvecell quantityVSAvoidculture time
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

The patent identifies and isolates NK1R+ mesenchymal stem cell precursors that already possess high proliferative capacity and therapeutic potential in their native state. By performing preliminary selection of these high-potency cells directly from bone marrow without requiring lengthy expansion cultures, the invention provides sufficient cell quantities for therapy while minimizing culture time and enabling immediate therapeutic use.

Inventive Principle:
Principle #10Preliminary action

3Ease of manufacture

If STRO-1 selected mesenchymal stem cells are used, then a specific cell population is obtained, but the cells lack known signaling involvement in disease and therapeutic efficacy is limited

Engineering Contradiction:
Improvecell selectionVSAvoidtherapeutic efficacy
Core Design Contradiction:
Ease of manufactureVSProductivity

Solution Approach 1:

The patent changes the selection parameter from STRO-1 expression to NK1R marker expression. This parameter change identifies a cell population with known signaling involvement in disease processes, particularly in pain and inflammatory conditions. The NK1R+ cells demonstrate superior therapeutic efficacy compared to STRO-1 selected cells while maintaining ease of manufacture through antibody-based selection methods.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS11642377B2Bone marrow derived neurokinin-1 receptor positive (NK1R+) mesenchymal stem cells for therapeutic applications
Publication Date: 2023.05.09 BIOCARDIA INC
  • US11642377B2 patent drawing
  • US11642377B2 patent drawing
  • US11642377B2 patent drawing

AI summary

The present disclosure provides use of neurokinin 1 receptor (NK1R) as a marker for identifying and/or isolating multipotential cells. The present disclosure provides cell populations enriched by methods of the present disclosure and therapeutic uses of these cells and agents derived from these cells.