Layered Cell Sheet Using Gelatin Hydrogel Particles
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Solution Overview
Problem
Existing cell sheet transplantation therapies face challenges in maintaining cell viability and function due to oxygen and nutrient supply limitations, particularly in thicker layers, leading to reduced engraftment and cardiac function recovery post-myocardial infarction.
Innovation Solution
The use of gelatin hydrogel particles, specifically with particle sizes of 20-32 µm, is introduced between cell layers to enhance oxygen and nutrient diffusion, allowing for the successful layering of 4 or more cell sheets and improving cell sheet thickness and function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If thicker cell sheets are produced to increase cardiomyocyte content, then the number of engrafted cells increases, but oxygen and nutrient supply becomes insufficient leading to cell death
Solution Approach 1:
The patent incorporates gelatin hydrogel particles with porous structure into the cell sheet to create channels for oxygen and nutrient diffusion, enabling thicker sheets to maintain cell viability throughout the entire thickness while increasing cardiomyocyte content
2Productivity
If more layers of cell sheets are transplanted to increase therapeutic effect, then cardiomyocyte replacement efficiency improves, but oxygen and nutrient diffusion becomes limited
Solution Approach 1:
Gelatin hydrogel particles serve as intermediary substances between cell layers, facilitating oxygen and nutrient diffusion through their porous structure, thereby enabling successful transplantation of multiple layers without compromising cell survival
3Quantity of substance
If cell sheets are layered without blood vessels to increase cell density, then engraftment quantity increases, but cell viability decreases due to poor oxygen supply
Solution Approach 1:
The porous gelatin hydrogel particles create artificial diffusion pathways that compensate for the absence of blood vessels, allowing oxygen and nutrients to reach high-density cell regions that would otherwise be inaccessible
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
This method significantly increases cell survival and function in layered cell sheets, enabling effective cell replacement therapies by ensuring adequate oxygen and nutrient supply, thereby enhancing cardiac function post-transplantation.
Implementation Method 1
inclusion of particles of the gel in aggregates of cultured cells, for example, has been reported to improve oxygen supply, etc., and thus the condition of cells
Data Source
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AI summary
The present invention relates to layered cell sheets comprising living cells and methods for producing the same. Specifically, the present invention provides methods for layering cell sheets, comprising layering cell sheets using hydrogel or preferably gelatin hydrogel. The present invention also provides layered cell sheets produced by such methods, and pharmaceutical compositions or therapeutic agents comprising layered cell sheets.