Donor and recipient hematopoietic stem and progenitor cells mobilization in liver transplantation patients

TL;DR

This study examines how hematopoietic stem and progenitor cells (HSPCs) mobilize in liver transplant patients, finding that high preoperative HSPC levels predict rejection and that HSPCs move to target tissues during immune responses.

Contribution

The study reveals the dynamic mobilization of donor and recipient HSPCs during alloresponses in liver transplant patients.

Findings

Patients who developed rejection had higher preoperative HSPC levels compared to healthy controls.

HSPC ratios decreased after transplantation and showed biased differentiation under immunosuppressive treatment.

Recipient and donor HSPCs mobilized during rejection and graft-versus-host disease episodes, respectively.

Abstract

Hematopoietic stem and progenitor cells (HSPCs) mobilize from bone marrow to peripheral blood in response to stress. The impact of alloresponse-induced stress on HSPCs mobilization in human liver transplantation (LTx) recipients remains under-investigated.

Peripheral blood mononuclear cell (PBMC) samples were longitudinally collected from pre- to post-LTx for one year from 36 recipients with acute rejection (AR), 74 recipients without rejection (NR), and 5 recipients with graft-versus-host disease (GVHD). 28 PBMC samples from age-matched healthy donors were collected as healthy control (HC). Multi-color flow cytometry (MCFC) was used to immunophenotype HSPCs and their subpopulations. Donor recipient-distinguishable major histocompatibility complex (MHC) antibodies determined cell origin.

Before LTx, patients who developed AR after transplant contained more HSPCs in PBMC samples than HC, while the NR group patients contained fewer HSPCs than HC. After LTx, the HSPC ratio in the AR group sharply decreased and became less than HC within six months, and dropped to a comparable NR level afterward. During the one-year follow-up period, myeloid progenitors (MPs) biased differentiation was observed in all LTx recipients who were under tacrolimus-based immunosuppressive treatment. During both AR and GVHD episodes, the recipient-derived and donor-derived HSPCs mobilized into the recipient’s blood-circulation and migrated to the target tissue, respectively. The HSPCs percentage in blood reduced after the disease was cured.

A preoperative high HSPC ratio in blood characterizes recipients who developed AR after LTx. Recipients exhibited a decline in blood-circulating HSPCs after transplant, the cells mobilized into the blood and migrated to target tissue during alloresponse.

The online version contains supplementary material available at 10.1186/s13287-024-03855-5.

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