Intrafemoral Injection of Human Hematopoietic Stem and Progenitor Cells into Immunocompromised Mice

Emily  F. Calderbank; Laura Magnani; Elisa Laurenti

doi:10.3791/66315

Injection intrafémorale de cellules souches et progénitrices hématopoïétiques humaines chez des s...

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Intrafemoral Injection of Human Hematopoietic Stem and Progenitor Cells into Immunocompromised Mice

Injection intrafémorale de cellules souches et progénitrices hématopoïétiques humaines chez des souris immunodéprimées

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03:40 min

December 8, 2023

DOI: 10.3791/66315-v

Emily F. Calderbank¹, Laura Magnani¹, Elisa Laurenti¹

¹Wellcome and Medical Research Council Cambridge Stem Cell Institute, Department of Haematology,University of Cambridge

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Overview

This study investigates the dynamics of hematopoietic stem and progenitor cells (HSPCs) across human development, utilizing intrafemoral injection in immunodeficient mice to enhance cell engraftment. By placing HSPCs directly into the bone marrow, the research aims to improve our understanding of normal blood cell development and the influence of age and disease.

Key Study Components

Research Area

Stem cell biology
Human hematopoiesis
Disease modeling

Background

Healthy human hematopoiesis is studied from fetal stages to elderly.
Understanding the healthy context aids in deciphering disease mechanisms.
Transplantation experiments provide functional insights into stem cell behavior.

Methods Used

Intrafemoral injection of human HSPCs
Immunodeficient mouse model
Cell culturing and preparation techniques

Main Results

Direct injection leads to higher stem cell engraftment.
Provides a quantitative perspective on aging and stem cell function.
Highlights the impact of external factors like inflammation on stem cells.

Conclusions

The study demonstrates effective methods for HSPC engraftment.
Offers insights into blood stem cell evolution and disease predisposition.

Frequently Asked Questions

What is the significance of HSPCs in blood formation?

HSPCs are essential for the formation of all types of blood cells throughout an individual's life.

Why use intrafemoral injections?

This method bypasses the homing phase, allowing for better engraftment of stem cells directly into the bone marrow.

What are the implications of this research for aging?

Understanding how HSPCs function over time can help identify how age-related diseases develop.

How does inflammation affect HSPCs?

Inflammation can alter the function and behavior of HSPCs, potentially leading to diseases.

What are the expected outcomes of the intrafemoral injection?

Higher engraftment rates and more reliable data on HSPC function compared to traditional methods.

Can this method be applied to other cell types?

While primarily used for HSPCs, similar techniques could potentially be adapted for other cell types.

What future research directions does this work suggest?

Future studies could explore the effects of various conditions on HSPC function and health across different age groups.

Les injections intrafémorales permettent la greffe d’un petit nombre de cellules souches et progénitrices hématopoïétiques (HSPC), en plaçant les cellules directement dans la cavité de la moelle osseuse. Nous décrivons ici un protocole expérimental d’injection intrafémorale de HSPC humaines chez des souris immunodéficientes.

Nous nous intéressons à l’étude de l’hématopoïèse humaine saine tout au long de la vie, du fœtus à la personne âgée. Par exemple, nous étudions le foie chez le fœtus et la moelle osseuse et le sang périphérique chez l’adulte. Nous pensons qu’il est important d’étudier le contexte sain pour nous aider à comprendre ce qui ne va pas dans la maladie.

Il existe de nombreuses approches Onyx sur cellule unique qui ont fait progresser le domaine ces dernières années, mais celles-ci fonctionnent parallèlement plutôt qu’à remplacer les expériences de transplantation qui testent la fonction des cellules souches. En injectant des cellules souches et progénitrices sanguines directement dans le fémur, nous contournons la phase de retour des injections intraveineuses. Les cellules sont déjà dans leur environnement naturel, et nous avons donc souvent une greffe beaucoup plus élevée.

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Mots-clés: Cellules souches hématopoïétiques CSH cellules souches et progénitrices hématopoïétiques CPH xénotransplantation injection intrafémorale souris immunodéprimées moelle osseuse greffe cytométrie en flux types de cellules sanguines