PMID- 34927242
OWN - NLM
STAT- MEDLINE
DCOM- 20220214
LR  - 20220731
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 196
IP  - 3
DP  - 2022 Feb
TI  - Identification of the minimum requirements for successful haematopoietic stem 
      cell transplantation.
PG  - 711-723
LID - 10.1111/bjh.17867 [doi]
AB  - Historically, defining haematopoietic subsets, including self-renewal, 
      differentiation and lineage restriction, has been elucidated by transplanting a 
      small number of candidate cells with many supporting bone marrow (BM) cells. 
      While this approach has been invaluable in characterising numerous distinct 
      subsets in haematopoiesis, this approach is arguably flawed. The haematopoietic 
      stem cell (HSC) has been proposed as the critical haematopoietic subset necessary 
      for transplantation. However, due to the presence of supporting cells, the HSC 
      has never demonstrated sufficiency. Utilising the homeobox B5 (Hoxb5)-reporter 
      system, we found that neither long-term (LT) HSCs nor short-term (ST) HSCs alone 
      were sufficient for long-term haematopoietic reconstitution. Critically, 
      reconstitution can be rescued by transplanting combined LT- and ST-HSCs, without 
      supporting cells; a fraction we term the 'Minimum Subset for Transplantation' 
      (MST). The MST accounts for only 0.005% of nucleated cells within mouse BM, and 
      this MST can be cultured, expanded and genetically modified while preserving its 
      rapid haematopoietic engraftment potential. These results support the 
      consideration of an MST approach for clinical translation, especially for gene 
      therapy approaches that require HSC compartment modification.
CI  - (c) 2021 The Authors. British Journal of Haematology published by British Society 
      for Haematology and John Wiley & Sons Ltd.
FAU - Nishi, Katsuyuki
AU  - Nishi K
AD  - RIKEN Centre for Biosystems Dynamics Research, Kobe, Hyogo, Japan.
AD  - Department of Hematology and Oncology, Graduate School of Medicine, Kyoto 
      University, Kyoto, Kyoto, Japan.
FAU - Sakamaki, Taro
AU  - Sakamaki T
AD  - RIKEN Centre for Biosystems Dynamics Research, Kobe, Hyogo, Japan.
FAU - Sadaoka, Kay
AU  - Sadaoka K
AD  - RIKEN Centre for Biosystems Dynamics Research, Kobe, Hyogo, Japan.
FAU - Fujii, Momo
AU  - Fujii M
AD  - RIKEN Centre for Biosystems Dynamics Research, Kobe, Hyogo, Japan.
FAU - Takaori-Kondo, Akifumi
AU  - Takaori-Kondo A
AD  - Department of Hematology and Oncology, Graduate School of Medicine, Kyoto 
      University, Kyoto, Kyoto, Japan.
FAU - Chen, James Y
AU  - Chen JY
AD  - Division of Oncology, Department of Medicine, Stanford University School of 
      Medicine, Stanford, CA, USA.
AD  - Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 
      Boston, MA, USA.
FAU - Miyanishi, Masanori
AU  - Miyanishi M
AUID- ORCID: 0000-0002-0527-3652
AD  - RIKEN Centre for Biosystems Dynamics Research, Kobe, Hyogo, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211220
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Biomarkers)
SB  - IM
MH  - Animals
MH  - Biomarkers
MH  - Cell Count
MH  - Cell Differentiation
MH  - Cell Lineage
MH  - Cell Tracking
MH  - Gene Expression
MH  - Genes, Reporter
MH  - Graft Survival
MH  - Hematopoiesis
MH  - *Hematopoietic Stem Cell Transplantation/methods/standards
MH  - Hematopoietic Stem Cells/cytology/metabolism
MH  - Humans
MH  - Mice
MH  - Models, Animal
MH  - Outcome Assessment, Health Care/*standards
MH  - Phenotype
MH  - *Quality Indicators, Health Care
MH  - Transplantation Conditioning
PMC - PMC9300074
OTO - NOTNLM
OT  - gene therapy
OT  - homeobox B5 (Hoxb5)
OT  - long-term haematopoietic stem cell
OT  - purified haematopoietic stem cell transplantation
OT  - short-term haematopoietic stem cell
COIS- The authors declare no conflicts of interest in association with the present 
      study.
EDAT- 2021/12/21 06:00
MHDA- 2022/02/15 06:00
PMCR- 2022/07/20
CRDT- 2021/12/20 06:32
PHST- 2021/09/15 00:00 [revised]
PHST- 2021/07/18 00:00 [received]
PHST- 2021/09/17 00:00 [accepted]
PHST- 2021/12/21 06:00 [pubmed]
PHST- 2022/02/15 06:00 [medline]
PHST- 2021/12/20 06:32 [entrez]
PHST- 2022/07/20 00:00 [pmc-release]
AID - BJH17867 [pii]
AID - 10.1111/bjh.17867 [doi]
PST - ppublish
SO  - Br J Haematol. 2022 Feb;196(3):711-723. doi: 10.1111/bjh.17867. Epub 2021 Dec 20.