Hypothermic Machine Perfusion for Islet Yield and Integrity
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Solution Overview
Problem
Current methods for isolating pancreatic islets for diabetes treatment face challenges such as low yield, quality issues, and reliance on human donor organs, which are scarce and inefficiently sourced, with porcine islets being particularly difficult to isolate due to fragility and fragmentation during processing.
Innovation Solution
The use of hypothermic machine perfusion (HMP) to develop interstitial edema in donor tissues, allowing for increased cellular product yield and quality by optimizing perfusion flow rates, pressures, and solution compositions, while preserving tissue integrity, and employing perfluorochemicals for improved oxygen delivery and cytoprotective agents to enhance islet preservation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If enzymatic digestion processes are used to isolate islets from donor pancreata, then islets can be released for further processing, but the digestive process is difficult to control and yields suboptimal quantities of viable cells
Solution Approach 1:
The patent changes the physical state parameters of the tissue by inducing controlled edema through hypothermic machine perfusion, altering tissue density and fluid content to facilitate islet separation without relying on uncontrolled enzymatic digestion
Solution Approach 2:
The patent extracts islets from the pancreatic tissue by creating density differences through edema formation, allowing islets to be separated from the edematous tissue matrix through density gradient centrifugation
2Adaptability or versatility
If porcine islets are isolated using conventional methods, then alternative donor source is available, but islets fragment during isolation and culture due to fragility
Solution Approach 1:
The patent applies hypothermic machine perfusion before isolation to induce controlled edema that acts as a cushioning effect, protecting islets from mechanical stress and fragmentation during subsequent processing steps
Solution Approach 2:
The patent changes the tissue physical properties by inducing edema, which alters the mechanical characteristics of the pancreatic tissue to reduce islet fragility and improve survival during isolation and culture
3Reliability
If human donor organs are relied upon for islet isolation, then clinical treatment can be provided, but the supply is inadequate and sourcing is inefficient
Solution Approach 1:
The patent makes the machine perfusion technology universally applicable to multiple donor sources including both human and porcine pancreata, enabling the system to treat different tissue types and donor origins with a single platform
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
HMP significantly increases the quantity and quality of isolated islets, reducing fragmentation and preserving functional integrity, enabling more efficient islet transplantation and addressing the scarcity of human donor organs by improving porcine islet isolation.
Implementation Method 1
developing edema during perfusion of the donor tissue to form a swelled tissue
Implementation Method 2
increasing a first perfusion pressure applied by the perfusion apparatus to the tissue to achieve a second perfusion pressure
Implementation Method 3
employing perfluorochemicals for improved oxygen delivery
Implementation Method 4
The use of hypothermic machine perfusion (HMP) to develop interstitial edema in donor tissues
Implementation Method 5
cytoprotective agents to enhance islet preservation
Data Source
AI summary
Methods of isolating cellular products, such as pancreatic islets, may be used in diabetes research and therapeutic transplantation. The methods may involve providing a donor tissue having desired cells and undesired cells, perfusing the donor tissue with a perfusion solution, developing edema during perfusion of the donor tissue to form a swelled tissue, and separating the desired cells from undesired cellular material to obtain a cellular product. The methods may also include disrupting the tissue, and separating the desired cells from undesired cellular material to obtain the cellular product. The methods may result in an increased yield of cellular product that retains sufficient functional integrity to be useful as a transplantation resource.