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Bone Marrow Transplantation Procedures in Mice to Study Clonal Hematopoiesis
Published on: May 26, 2021
Pediatric bone marrow microenvironment before and after allogeneic hematopoietic stem cell transplantation: a
Pan Zhang1,2, Ang Wei3,4,5,6,7, Guanghua Zhu3,4,5,6,7
1Department of Stem cell Transplantation, Baoding Hospital of Beijing Children's Hospital, Capital Medical University, Baoding, 071000, China.
Insights
Pediatric bone marrow has better hematopoietic stem cell regeneration and less oxidative stress than adult marrow. Lower endothelial progenitor cell proportions are linked to poor graft function after HSCT in children.
Area of Science:
- Hematology
- Pediatric Oncology
- Stem Cell Transplantation
Background:
- The bone marrow microenvironment is crucial for hematopoietic stem cell (HSC) function.
- Differences in the pediatric versus adult bone marrow microenvironment are not fully understood.
- Understanding these differences may impact outcomes in pediatric hematopoietic stem cell transplantation (HSCT).
Purpose of the Study:
- To compare the bone marrow microenvironment in healthy children and adults.
- To investigate the association between the post-HSCT bone marrow microenvironment and graft function in pediatric HSCT recipients.
Main Methods:
- Retrospective analysis of pediatric HSCT patients and healthy adult donors.
- Bone marrow samples analyzed pre- and post-HSCT (Days 14-90).
- Measured percentages of endothelial progenitor cells (EPCs), hematopoietic stem cells (CD34+ HSCs), and reactive oxygen species (ROS) levels.
Main Results:
- Adult donors had lower HSC proportions and higher HSC-ROS levels than pediatric donors (0-6 years).
- Patients with good graft function (GGF) had significantly higher EPC proportions than those with poor graft function (PGF).
- An EPC proportion >0.071% post-HSCT predicted GGF (AUC=0.874).
Conclusions:
- Pediatric bone marrow niches exhibit superior hematopoietic regenerative capacity and reduced oxidative stress compared to adult niches.
- A lower proportion of EPCs in the bone marrow post-HSCT is associated with defective hematopoiesis and PGF in pediatric patients.
Abstract:
To compare the bone marrow microenvironment between healthy children and adults and investigate the association between the posttransplant bone marrow microenvironment and PGF in pediatric HSCT recipients. This retrospective study involved pediatric patients who underwent allogeneic-HSCT at Beijing Children's Hospital and Baoding Children's Hospital between January 2021 and June 2024. Bone marrow samples were collected before HSCT and between Days 14 and 90 post-HSCT to measure the percentages of endothelial progenitor cells (EPCs) and hematopoietic stem cells (CD34 + HSCs), as well as reactive oxygen species (ROS) levels. Selected donors were enrolled as controls, and their bone marrow samples were similarly assessed for those parameters. One hundred forty pediatric patients and 48 bone marrow donors were included in this study. Subsequent analysis revealed that adult donors had a significantly lower proportion of HSCs compared with the 0-6-year donors subgroup (0.865% (0.03, 2.21) vs. 3.38% (1.38, 5.23); U = 3.93, P < 0.001) and significantly higher HSC-ROS levels (1,979 (1,039, 5,166) vs. 977 (453, 1,597); U = 3.11, P = 0.002). The good graft function (GGF) group had a significantly greater proportion of EPCs compared with the poor graft function (PGF) group (0.106% (0.03-0.69) vs. 0.047%(0.015-0.09), U = 3.184, P = 0.001). Receiver operating characteristic (ROC) analysis revealed that an EPC proportion threshold > 0.071% in the bone marrow at 14-90 days post-transplantation predicted GGF outcomes (AUC = 0.874; 95% CI: 0.743-1.000). These findings suggest that compared with their adult counterparts, pediatric bone marrow niches possess superior hematopoietic regenerative capacity and reduced oxidative stress and that a lower proportion of EPCs is responsible for defective hematopoiesis in PGF pediatric patients.
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