Deceased Donor Blood Analysis for Mixed Chimerism
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Solution Overview
Problem
Current methods for establishing mixed chimerism in organ transplant recipients require hematopoietic stem and progenitor cells from living donors, which are challenging to obtain due to invasive procedures and limited supply, and immunosuppressive drugs are necessary to prevent rejection, carrying significant risks.
Innovation Solution
Development of new manufacturing processes for engineered hematopoietic cellular products derived from deceased donors, including new blood collection apparatuses, ex vivo extraction methods, and processing techniques to isolate CD34+ and CD3+ cells from bone marrow and blood, respectively, allowing for the creation of cellular compositions that promote mixed chimerism without the need for living donors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If HSPCs are collected from living donors by surgical extraction, then sufficient quantity of HSPCs can be obtained, but the procedure involves general anesthesia, pain, and risk of infection or damage to nerves and muscles
Solution Approach 1:
The patent inverts the traditional approach by using deceased donors instead of living donors for HSPC collection. This reversal eliminates the harmful effects on living individuals (anesthesia risks, pain, nerve damage) while still providing sufficient HSPCs through bone marrow extraction from deceased donors. The procedure is performed after death, converting a harmful living procedure into a beneficial post-mortem utilization.
Solution Approach 2:
The patent introduces an intermediary approach by using deceased donors as a bridge between the need for HSPCs and the avoidance of harm to living persons. Deceased donors serve as an intermediary source that satisfies the quantitative requirement for HSPCs without imposing the harmful effects associated with living donor procedures.
2Object-affected harmful factors
If HSPCs are recovered non-surgically by apheresis, then the procedure avoids surgery and anesthesia, but it can take up to six hours, may need to be repeated for several days, and poses a risk of infection and blood clotting
Solution Approach 1:
The patent inverts the approach by moving from living donor apheresis to deceased donor bone marrow extraction. This reversal eliminates the time-consuming nature of apheresis (which may require 6 hours per session over several days) while still avoiding the harms of surgical extraction and anesthesia. The HSPCs are obtained in a single procedure performed after death.
3Quantity of substance
If HSPCs are obtained from deceased donors, then the supply limitation and harm to living donors are avoided, but new challenges arise in collecting and processing blood from deceased donors
Solution Approach 1:
The patent applies segmentation by dividing the blood collection and processing into distinct modular components: (1) blood collection apparatus with specific needles and containers, (2) separation processes to isolate HSPCs from other blood components, and (3) processing steps to prepare the cells for transplantation. This segmentation makes the complex overall process more manageable and systematic.
Solution Approach 2:
The patent employs preliminary action by preparing the blood collection system and processing protocols in advance for deceased donors. The blood collection apparatus is designed and ready before donation, and processing protocols are established beforehand to handle the unique challenges of post-mortem blood collection, including timing constraints and cell viability maintenance.
Data Source
AI summary
The invention provides cellular compositions that contain CD34+ cells derived from bone marrow of a decease donor and CD3+ cells derived from non-bone marrow of the deceased donor. The compositions are useful to promote mixed chimerism in recipients of solid organ transplants. The invention also provides methods of making and using such compositions. In certain embodiments, the invention further provides methods of analyzing and preparing blood and blood components from a deceased donor for use in compositions of the invention to promote mixed chimerism in solid organ transplant recipients.