Pulsatile Placental Perfusion for Stem Cell Recovery

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Solution Overview

Problem

Current methods for collecting umbilical cord blood stem cells are inefficient, resulting in insufficient cell numbers for adult transplants, leading to delayed engraftment or failure, and the discarding of residual cells from the placenta, which could be used for regenerative medicine.

Innovation Solution

A method involving pulsatile machine placental perfusion (PMPP) to collect cord blood stem cells from the placenta, which can be combined with conventional methods, using a perfusion solution to flush out stem cells without the need for anticoagulants, allowing for increased recovery of primitive hematopoietic stem cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional needle/syringe withdrawal or gravity drainage collection is used, then the collection process is simple, but the number of stem cells recovered is insufficient

Engineering Contradiction:
Improvenumber of stem cellsVSAvoidcollection method complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent applies hydraulic principles by using a machine pulsatile perfusion system that pumps perfusion solution through the placental tissue. The system uses a pump to create pulsatile flow, forcing the perfusion solution through placental vessels to dislodge and collect residual cord blood stem cells that conventional methods miss. This hydraulic approach enables recovery of significantly more stem cells (increasing CD34+ cell count by 2-3 times) while using standardized medical equipment.

Inventive Principle:
Principle #29Pneumatics and hydraulics

2Quantity of substance

If residual placenta cord blood cells are discarded, then the collection process is quick and simple, but valuable stem cells are lost

Engineering Contradiction:
Improvestem cell recoveryVSAvoidcollection time
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

The patent implements continuous useful action by performing pulsatile perfusion immediately after conventional cord blood collection, without discarding the placenta. The system continuously pumps perfusion solution through the placenta to extract residual stem cells, maximizing recovery from the same tissue source. This sequential process converts previously discarded material into a valuable additional cell source, effectively doubling or tripling total stem cell recovery while adding only minimal time to the overall process.

Inventive Principle:
Principle #20Continuity of useful action

3Reliability

If anticoagulants are injected into the placenta, then clotting is prevented, but the procedure becomes more complex and requires preparation

Engineering Contradiction:
Improveclot preventionVSAvoidprocedure simplicity
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent uses the perfusion solution itself as an intermediary carrier that contains anticoagulant properties. Rather than injecting anticoagulants directly into the placenta tissue, the anticoagulated perfusion solution flows through the placental vessels, preventing clotting during the perfusion process. This approach combines the anticoagulant function with the perfusion medium, eliminating the need for separate anticoagulant injection steps while maintaining reliable clot prevention throughout the cell collection process.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 achieves a significant increase in the number of stem cells, particularly CD34+ and CD133+ cells, enabling more effective stem cell banking and potential for multiple uses in regenerative medicine and reducing the need for multiple donor grafts.

Implementation Method 1

subjecting the partially exsanguinated placenta to a pressure-mediated flow of perfusion solution

Methodology Applied
Scientific EffectPressure-mediated flow: Pressure Gradient

Implementation Method 2

the pressure-mediated flow of perfusion solution comprises a pulsatile flow of perfusion solution

Methodology Applied
Scientific EffectPulsatile flow: Pulse Jet

Data Source

PatentEP3603390B1Methods for collecting and using placenta cord blood stem cells
Publication Date: 2023.12.20 CELULARITY INC
  • EP3603390B1 patent drawingFigure 1
  • EP3603390B1 patent drawingFigure 2
  • EP3603390B1 patent drawingFigure 3

AI summary

An innovative method of collecting cord blood stern cells from an isolated mammalian non-exsanguinated or partially exsanguinated placenta by placental perfusion is described. Placental perfusion can include perfusing the isolated placenta with a pulsatile flow of perfusion solution, for example, using a pulsatile or peristaltic pump or device. The stem cells can then be isolated from the perfusate. The perfusion solution can include an anticoagulant. The isolated mammalian placenta need not be treated with an anticoagulant prior to perfusing. The isolated placenta can be free from an anticoagulant prior to perfusing.