Parathyroid Hormone Mobilizes Stem Cells for Ischemic Tissue Repair

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Solution Overview

Problem

Current treatments for ischemic heart diseases lack effective and economical means to recruit stem cells for tissue repair and regeneration, with existing methods having limited duration and efficiency in mobilizing stem cells to ischemic tissues.

Innovation Solution

The use of parathyroid hormone (PTH) or its fragments, potentially combined with DPP IV antagonists, to mobilize stem cells from the bone marrow into ischemic tissues, enhancing their homing and survival, thereby promoting tissue repair and regeneration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If conventional stem cell mobilization methods are used, then stem cells can be mobilized to ischemic tissues, but the duration and efficiency of mobilization are limited

Engineering Contradiction:
Improveduration of stem cell mobilizationVSAvoidefficiency of stem cell mobilization
Core Design Contradiction:
Duration of action of moving objectVSProductivity

Solution Approach 1:

The patent changes the parameter of mobilization duration by using PTH treatment protocols that sustain stem cell mobilization for extended periods (up to 4 weeks) compared to conventional transient mobilization methods, thereby resolving the contradiction between duration and efficiency

Inventive Principle:
Principle #35Parameter changes

2Reliability

If stem cell mobilization is enhanced, then tissue repair is improved, but the cost and complexity of treatment increase

Engineering Contradiction:
Improvetissue repair effectivenessVSAvoidtreatment complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent uses PTH as an intermediary substance that naturally mediates stem cell mobilization and homing to ischemic tissues, providing a biologically-based treatment that enhances tissue repair effectiveness while avoiding the complexity of synthetic or mechanical intervention systems

Inventive Principle:
Principle #24Intermediary (Mediator)

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

PTH treatment significantly increases stem cell mobilization and improves myocardial function, survival, and reduces arterial resistance, leading to enhanced tissue repair and regeneration in ischemic tissues, with prolonged benefits up to four weeks post-treatment.

Implementation Method 1

Parathyroid hormone is well known as one of the two major hormones modulating calcium and phosphate homeostasis. It is responsible for maintaining serum ionized calcium concentrations within a narrow range, through its action to stimulate renal tubular calcium reabsorption and bone resorption.

Methodology Applied
Scientific EffectHormone-receptor binding:

Implementation Method 2

It is responsible for maintaining serum ionized calcium concentrations within a narrow range, through its action to stimulate renal tubular calcium reabsorption and bone resorption.

Methodology Applied
Scientific EffectBone resorption:

Implementation Method 3

It is responsible for maintaining serum ionized calcium concentrations within a narrow range, through its action to stimulate renal tubular calcium reabsorption and bone resorption.

Methodology Applied
Scientific EffectCalcium reabsorption:

Implementation Method 4

On a more chronic basis, parathyroid hormone also stimulates the conversion of calcidiol to calcitriol in renal tubular cells, thereby stimulating intestinal calcium absorbtion

Methodology Applied
Scientific EffectHormonal conversion:

Implementation Method 5

The pharmaceutical composition comprising PTH or PTH fragments is used for recruiting stem cells into tissue suffering from ischemia, wherein said stem cells are preferably capable of repairing and/or regenerating said tissue suffering from ischemia.

Methodology Applied
Scientific EffectCell homing:

Data Source

PatentEP2007416B1Paratyroid hormone (PTH) for use in the treatment of ischemia
Publication Date: 2017.09.27 LUDWIG MAXIMILIANS UNIV MUNCHEN
  • EP2007416B1 patent drawingFigure 1A~1B
  • EP2007416B1 patent drawingFigure 2A~2B
  • EP2007416B1 patent drawingFigure 3A~3B

AI summary

The present invention relates to uses and methods of parathyroid hormone (PTH), preferably PTH (1-34), and/or parathyroid hormone-related peptide (PTHrP), preferably PTHrP (1-34), for recruiting stem cells into tissue suffering from ischemia, wherein said stem cells are preferably capable of repairing and/or regenerating said tissue suffering from ischemia. Accordingly, the uses and methods of the present invention are preferably suitable for the prevention and/or treatment of ischemia. Moreover, the present invention relates to a composition comprising parathyroid hormone (PTH), preferably PTH (1-34), and/or parathyroid hormone-related peptide (PTHrP), preferably PTHrP (1-34), and/or G-CSF or a G-CSF fragment for use as a pharmaceutical composition. In a particular aspect, a DPP IV antagonist is applied in the uses, methods and/or compositions of the present invention.