Hematopoietic Stem Cell Engraftment via Ex Vivo Compound Treatment

Solution Overview

Problem

Hematopoietic stem and progenitor cell engraftment failures occur due to micro-environmental defects, stromal cell damage, and graft-versus-host disease, leading to inadequate long-term engraftment and hematopoietic recovery in hematologic disorders and cancer treatments.

Innovation Solution

The use of specific compounds such as 1,2-didecanoyl-glycerol, 11,12 Epoxyeicosatrienoic acid, 1-hexadecyl-2arachidonoyl glycerol, 6-formylindolo[3,2-B]carbazole, 9-cis-retinoic acid, anandamide, carbacyclin, clofibrate, carbamyl PAF, Prostaglandin B2, and 1,2-dioctanoyl-sn-glycerol to enhance hematopoietic cell engraftment by treating cells ex vivo or administering them to subjects undergoing transplantation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If hematopoietic stem and progenitor cell transplantation is performed to treat hematologic disorders and malignancies, then hematopoietic recovery can be achieved, but engraftment failures occur due to micro-environmental defects, stromal cell damage, and graft-versus-host disease

Engineering Contradiction:

Improveengraftment success rateVSAvoidmicro-environmental defects and stromal cell damage

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by treating hematopoietic stem and progenitor cells ex vivo with compounds (such as prostaglandins, PPAR agonists, or other specified agents) before transplantation to enhance their engraftment capacity. This pre-treatment prepares the cells to overcome micro-environmental defects and stromal cell damage in the recipient, thereby improving engraftment success rates without requiring additional interventions after transplantation.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses chemical compounds (intermediaries) such as prostaglandins, PPAR agonists, or other specified agents to mediate between the transplanted hematopoietic cells and the recipient's micro-environment. These compounds act as messengers that improve cell survival, homing, and integration, thereby overcoming harmful factors like micro-environmental defects and stromal cell damage without directly modifying the recipient's environment.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Duration of action of moving object

If conventional transplantation methods are used, then the procedure is simple, but long-term engraftment fails due to lack of cellular engraftment of hematopoietic stem cells

Engineering Contradiction:

Improvelong-term engraftmentVSAvoidcellular engraftment efficiency

Core Design Contradiction:

Duration of action of moving objectVSReliability

Solution Approach 1:

The patent applies preliminary action by treating hematopoietic stem and progenitor cells ex vivo with compounds (such as prostaglandins, PPAR agonists, or other specified agents) before transplantation to enhance their engraftment capacity. This pre-treatment prepares the cells to overcome micro-environmental defects and stromal cell damage in the recipient, thereby improving engraftment success rates without requiring additional interventions after transplantation.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent applies parameter changes by modifying the biological state of hematopoietic cells through chemical treatment (changing concentration, viability, or differentiation parameters) before transplantation. This alters key parameters of the cells to improve their survival and engraftment efficiency in the recipient, directly addressing the failure of long-term engraftment.

Inventive Principle:

Principle #35Parameter changes

3Productivity

If no compound treatment is applied, then the transplantation procedure is straightforward, but engraftment efficiency is insufficient for adequate hematopoietic recovery

Engineering Contradiction:

Improveengraftment efficiencyVSAvoidcompound treatment protocol

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by treating hematopoietic stem and progenitor cells ex vivo with compounds (such as prostaglandins, PPAR agonists, or other specified agents) before transplantation to enhance their engraftment capacity. This pre-treatment prepares the cells to overcome micro-environmental defects and stromal cell damage in the recipient, thereby improving engraftment success rates without requiring additional interventions after transplantation.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses chemical compounds (intermediaries) such as prostaglandins, PPAR agonists, or other specified agents to mediate between the transplanted hematopoietic cells and the recipient's micro-environment. These compounds act as messengers that improve cell survival, homing, and integration, thereby overcoming harmful factors like micro-environmental defects and stromal cell damage without directly modifying the recipient's environment.

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS10092599B2Methods for enhancing hematopoietic stem/progenitor cell engraftment

Publication Date: 2018.10.09 CHILDRENS MEDICAL CENT CORP

AI summary

Described herein are methods for enhancing engraftment of hematopoietic stem and progenitor cells using compounds identified using a zebrafish model of hematopoietic cell engraftment. The compounds can be used to treat hematopoietic stem cells ex vivo prior to transplantation of the cells. Alternatively, the compounds can be administered to an individual undergoing cell transplantation.