Umbilical Cord Cell Fraction Selection for Transplantation
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Solution Overview
Problem
Current methods for umbilical cord blood transplantation are limited by the low stem cell dose, leading to delayed engraftment and increased transplant-related complications due to inadequate hematopoietic recovery, particularly in adults, where the availability of suitably HLA-matched donors is a significant challenge.
Innovation Solution
A method for selecting and ex-vivo expanding CD133+/CD34+ cord blood cells using cytokines and nicotinamide, which enhances cell proliferation, viability, and homing to the bone marrow, while maintaining self-renewal capacity, and separating these cells from CD133/CD34 negative fractions for transplantation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cord blood is used for transplantation, then availability and safety are improved, but stem cell dose is insufficient
Solution Approach 1:
The patent applies preliminary action by performing ex-vivo expansion of cord blood stem cells before transplantation. The method involves culturing CD133+CD34+ cells with specific cytokines (SCF, TPO, FLT-3L, IL-6) and nicotinamide to increase cell numbers prior to transplantation, thereby resolving the contradiction between safety and insufficient cell dose
Solution Approach 2:
The patent applies parameter changes by optimizing culture conditions including cytokine concentrations, nicotinamide dosage, and culture duration to achieve optimal cell expansion. These parameter adjustments enable significant increase in stem cell dose while maintaining cell quality and safety for transplantation
2Quantity of substance
If dual cord blood transplantation is performed, then stem cell dose is increased, but engraftment kinetics are not improved
Solution Approach 1:
The patent applies preliminary action by pre-expanding stem cells ex-vivo before transplantation, so that sufficient cell numbers are achieved without requiring dual cord blood units. This preliminary expansion maintains rapid engraftment kinetics while avoiding the complications of dual transplantation
Solution Approach 2:
The patent uses ex-vivo culture conditions including cytokines and nicotinamide as intermediaries to facilitate cell expansion and maintain engraftment potential. These intermediaries enable single cord blood unit expansion without compromising engraftment kinetics
3Quantity of substance
If ex-vivo expansion is performed, then stem cell numbers are increased, but cell differentiation increases
Solution Approach 1:
The patent applies parameter changes by using nicotinamide in the culture medium to maintain stem cell properties during expansion. This parameter adjustment prevents excessive differentiation while achieving the desired increase in stem cell numbers for transplantation
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 approach increases the number of hematopoietic progenitor cells, improves engraftment efficacy, and reduces differentiation, resulting in rapid and robust engraftment, thereby reducing transplant-related complications and mortality.
Implementation Method 1
culturing CD133+ cord blood cells in the presence of cytokines (SCF, TPO, IL-6 and FLT-3 ligand) and nicotinamide resulted in better and prolonged expansion of both late and early progenitors
Implementation Method 2
ex vivo expansion of cord blood stem cells... The aim of ex vivo expansion of cord blood is to provide a graft with sufficient numbers of cells
Implementation Method 3
CD34+ cells obtained following culturing with NAM displayed increased migration towards SDF-1 and home to the bone marrow (24 hour post infusion) with higher efficacy than cells cultured with cytokines only or non-cultured cells
Data Source
AI summary
Methods of selecting umbilical cord blood units for ex-vivo expansion, separation of CD133+/CD34+ positive and uncultured CD133+/CD34+ negative fractions, methods for expanding the selected CD133+/CD34+ fraction, selection of expanded populations of CD133+/CD34+ cord blood cells for transplantation to subjects in need thereof and the therapeutic use of suitable selected, ex-vivo expanded CD 133+/CD34+ and unselected CD133/CD34 negative cord blood fractions for transplantation in the clinical setting, for treatment of hematological malignancies are provided. The present invention also envisions kits comprising the expanded and unselected cord blood fractions.