Identification of Long-Term Repopulating Potential of Human Cord Blood-Derived CD34−flt3− Severe Combined Immunodeficiency-Repopulating Cells by Intra-Bone Marrow Injection

Kimura, Takafumi; Asada, Rumiko; Wang, Jianfeng; Kimura, Takashi; Morioka, Miho; Matsui, Kazuo; Kobayashi, Katsuya; Henmi, Kae; Imai, Shiro; Kita, Masakazu; Tsuji, Takashi; Sasaki, Yutaka; Ikehara, Susumu; Sonoda, Yoshiaki

doi:10.1634/stemcells.2006-0727

Cited by 40 publications

(69 citation statements)

References 54 publications

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“…It has been shown that MSCs can reconstitute the BM microenvironment after direct injection into the BM. 31,32 In addition, MSCs have been found in BM after systemic infusion in an animal model and can enhance the engraftment of HSCs. [33][34][35] These results suggest that MSCs can home to BM and support hematopoiesis.…”

Section: Discussionmentioning

confidence: 99%

Co-transplantation of third-party umbilical cord blood-derived MSCs promotes engraftment in children undergoing unrelated umbilical cord blood transplantation

Lee

Yoo

et al. 2013

Bone Marrow Transplant

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Success of umbilical cord blood transplantation (UCBT) has been limited by a high rate of graft failure and delayed hematological recovery. It has been postulated that MSCs have hematopoiesis-supportive properties. Therefore, to overcome the limitation of UCBT, third-party UCB-derived MSCs were co-transplanted in recipients receiving unrelated UCBT. Seven patients received UCB and third-party UCB-MSCs. Hematopoietic recovery and transplantation outcomes were compared with historic controls. There was no acute toxicity associated with the infusion of MSCs. The median day to neutrophil engraftment was 19 days in patients, as compared with 24 days in controls (P ¼ 0.03). The median day of platelet engraftment was 47 days and 57 days in patients and controls, respectively (P ¼ 0.26). In addition, there was no engraftment failure in the MSC group. The incidence of acute and chronic GVHD was comparable between the two groups. However, veno-occlusive disease and TRM did not occur in the MSC group. Thirdparty UCB-MSCs infusion was safe and feasible. MSCs may also enhance the engraftment of UCBT and prevent rejection. In addition, MSCs may have a role in decreasing TRM. Randomized, controlled trials are required to confirm these results and longer follow-up will determine the effects of MSCs on the risk of relapse.

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Section: Discussionmentioning

confidence: 99%

Co-transplantation of third-party umbilical cord blood-derived MSCs promotes engraftment in children undergoing unrelated umbilical cord blood transplantation

Lee

Yoo

et al. 2013

Bone Marrow Transplant

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“…The CB-derived lineage-negative (Lin À ) mononuclear cells were separated using a StemSep device (StemCell Technologies, Vancouver, BC, Canada), as reported earlier. [7][8][9] Purification of Lin À CD34 þ CD38 þ , Lin À CD34 þ CD38 À , and Lin À CD34 À cells…”

Section: Methodsmentioning

confidence: 99%

“…[7][8][9]13 In this study, purified 2.5 Â 10 3 to 2 Â 10 4 CB-derived Lin À CD34 þ CD38 þ , 20-4 Â 10 2 CBderived Lin À CD34 À CD38 À cells, or 2-7 Â 10 4 CB-derived Lin À CD34 À cells were transplanted by IBMI 7-9 into sublethally irradiated (250 cGy using a 137 Cs-g irradiator) 8-to 10-week-old NOD/SCID or NOG mice. The repopulation of human hematopoietic cells in murine BMs was serially analyzed by the aspiration method.…”

Section: Nod/scid and Nog Micementioning

confidence: 99%

“…7 Functional studies revealed that these CD34 À SRCs have different HSC characteristics from earlier-reported CD34 þ SRCs. [7][8][9] These data suggested that the CD34 À SRCs are a novel class of primitive repopulating HSCs that can only be detected by the sensitive IBMI method. [7][8][9][10] On the other hand, Hogan et al 11 clearly showed that CB-derived SRCs present in the CD34 þ cell fraction could be segregated into two subpopulations with distinct repopulation characteristics.…”

Section: Introductionmentioning

confidence: 97%

“…[7][8][9] These data suggested that the CD34 À SRCs are a novel class of primitive repopulating HSCs that can only be detected by the sensitive IBMI method. [7][8][9][10] On the other hand, Hogan et al 11 clearly showed that CB-derived SRCs present in the CD34 þ cell fraction could be segregated into two subpopulations with distinct repopulation characteristics. The CD34 þ CD38 þ SRCs could rapidly repopulate the recipient NOD/SCID mice, but they could only maintain a human cell repopulation for 12 weeks, while showing no secondary repopulating potential.…”

Section: Introductionmentioning

confidence: 97%

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In vivo dynamics of human cord blood-derived CD34− SCID-repopulating cells using intra-bone marrow injection

et al. 2009

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The identification of human CD34-negative (CD34 À ) hematopoietic stem cells (HSCs) provides a new concept for the hierarchy in the human HSC compartment. This study investigated the long-term repopulating capacity and redistribution kinetics of human cord blood-derived CD34 À severe combined immunodeficiency (SCID)-repopulating cells (SRCs) and compared them with those of CD34 þ CD38 þ and CD34 þ CD38 À SRCs using the intra-bone marrow injection (IBMI) to clarify the characteristics of CD34 À SRCs. On the basis of the limiting dilution analyses data, estimated numbers of CD34 þ CD38 þ , CD34 þ CD38 À , and CD34 À SRCs were transplanted to NOD/SCID mice by IBMI. The human cell repopulation at the site of injection and the other bones were serially investigated. Interestingly, CD34 þ CD38 þ , CD34 þ CD38 À , and CD34 À SRCs began to migrate to other bones 2 and 5 weeks after the transplantation, respectively. Accordingly, the initiation of migration seemed to differ between the CD34 þ and CD34 À SRCs. In addition, CD34 þ CD38 þ SRCs only sustained a shortterm repopulation. However, both CD34 þ CD38 À and CD34 À SRCs had longer-term repopulation capacity. Taken together, these findings showed that CD34 À SRCs show different in vivo kinetics, thus suggesting that the identified CD34 À SRCs are a distinct class of primitive HSCs in comparison to the CD34 þ CD38 þ and CD34 þ CD38 À SRCs.

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Prospectively Isolated Human Bone Marrow Cell-Derived MSCs Support Primitive Human CD34-Negative Hematopoietic Stem Cells

Matsuoka¹,

Nakatsuka²,

Sumide³

et al. 2015

Stem Cells

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Hematopoietic stem cells (HSCs) are maintained in a specialized bone marrow (BM) niche, which consists of osteoblasts, endothelial cells, and a variety of mesenchymal stem/stromal cells (MSCs).However, precisely what types of MSCs support human HSCs in the BM remain to be elucidated because of their heterogeneity. In this study, we succeeded in prospectively isolating/establishing three types of MSCs from human BM-derived lineage-and CD45-negative cells, according to their cell surface expression of CD271 and stage-specific embryonic antigen (SSEA)24. Among them, the MSCs established from the Lineage1 SSEA-4 1 fraction (DP MSC) could differentiate into osteoblasts and chondrocytes, but they lacked adipogenic differentiation potential. The DP MSCs expressed significantly higher levels of well-characterized HSC-supportive genes, including IGF-2, Wnt3a, Jagged1, TGFb3, nestin, CXCL12, and Foxc1, compared with other MSCs. Interestingly, these osteo-chondrogenic DP MSCs possessed the ability to support cord blood-derived primitive human CD34-negative severe combined immunodeficiency-repopulating cells. The HSCsupportive actions of DP MSCs were partially carried out by soluble factors, including IGF-2, Wnt3a, and Jagged1. Moreover, contact between DP MSCs and CD34-positive (CD34 1 ) as well as CD34-negative (CD34 2 ) HSCs was important for the support/maintenance of the CD34 1/2 HSCs in vitro. These data suggest that DP MSCs might play an important role in the maintenance of human primitive HSCs in the BM niche. Therefore, the establishment of DP MSCs provides a new tool for the elucidation of the human HSC/niche interaction in vitro as well as in vivo. STEM CELLS 2015;33:1554-1565

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Identification of Long-Term Repopulating Potential of Human Cord Blood-Derived CD34−flt3− Severe Combined Immunodeficiency-Repopulating Cells by Intra-Bone Marrow Injection

Abstract: Recently, we have identified human cord blood (CB)-derived CD34-negative (CD34 ؊ ) severe combined immunodeficiency (SCID)-repopulating cells (SRCs STEM CELLS 2007;25:1348 -1355 Disclosure of potential conflicts of interest is found at the end of this article.

Cited by 40 publications

References 54 publications

Co-transplantation of third-party umbilical cord blood-derived MSCs promotes engraftment in children undergoing unrelated umbilical cord blood transplantation

Co-transplantation of third-party umbilical cord blood-derived MSCs promotes engraftment in children undergoing unrelated umbilical cord blood transplantation

In vivo dynamics of human cord blood-derived CD34− SCID-repopulating cells using intra-bone marrow injection

Prospectively Isolated Human Bone Marrow Cell-Derived MSCs Support Primitive Human CD34-Negative Hematopoietic Stem Cells

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