Role of MAdCAM-1 and Its Ligand on the Homing of Transplanted Hematopoietic Cells in Irradiated Mice

Tada, Tatsuya; Inoue, N.; Widayati, Diah Tri; Fukuta, Katsuhiro

doi:10.1538/expanim.57.347

Cited by 10 publications

(9 citation statements)

References 38 publications

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“…3E). This is in agreement with previous studies demonstrating that antibody blocking of a4b7 integrin on donor WBM cells impedes cell rolling on the BM vasculature [26] and subsequently BM homing after transplant [26,28]. Altogether, we conclude that the impaired ability of b7KO HSCs to home into the BM of irradiated hosts after transplantation accounted for their reduced engraftment potential.…”

Section: Discussionsupporting

confidence: 93%

“…These data suggest that the activity of a4b7 integrin on HSCs was mediated through its specific interaction with its endothelial ligand MAdCAM-1 in the BM microenvironment. Additionally, because lethal irradiation also induces the expression of fibronectin and VCAM-1 on BM ECs [28,49], we cannot exclude the possibility that a4b7 integrin binding to these low-affinity ligands may also be involved in HSC homing to the BM.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have suggested a potential role for a4b7 integrin and MAdCAM-1 in HSC homing to the recipient's BM using cell lines and blocking antibodies. However, the use of a mixed population of HSPCs, not a purified HSC population, made it difficult to interpret their results [26,28]. Therefore, the homing of HSCs, committed progenitors and terminally differentiated mature hematopoietic cells cannot be distinguished from one another, and thus, whether or not the outcomes are the consequence of a direct effect on HSCs cannot be determined.…”

Section: Discussionmentioning

confidence: 99%

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Evidence that β7 Integrin Regulates Hematopoietic Stem Cell Homing and Engraftment Through Interaction with MAdCAM-1

Murakami

Franco

et al. 2016

Stem Cells and Development

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a4b7 integrin is a cell adhesion receptor that is crucial for the migration of hematopoietic progenitors and mature effector cells in the periphery, but its role in adult hematopoiesis is controversial. We identified a subset of hematopoietic stem cells (HSCs) in the bone marrow (BM) that expressed b7 integrin. These b7 + HSCs were capable of multilineage, long-term reconstitution and had an inherent competitive advantage over b7 -HSCs. On the other hand, HSCs that lacked b7 integrin (b7KO) had reduced engraftment potential. Interestingly, quantitative RT-PCR and flow cytometry revealed that b7KO HSCs expressed lower levels of the chemokine receptor CXCR4. Accordingly, b7KO HSCs exhibited impaired migration abilities in vitro and BM homing capabilities in vivo. Lethal irradiation induced expression of the a4b7 integrin ligand-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) on BM endothelial cells. Moreover, blocking MAdCAM-1 reduced the homing of HSCs and impaired the survival of recipient mice. Altogether, these data indicate that b7 integrin, when expressed by HSCs, interacted with its endothelial ligand MAdCAM-1 in the BM microenvironment, thereby promoting HSC homing and engraftment.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Evidence that β7 Integrin Regulates Hematopoietic Stem Cell Homing and Engraftment Through Interaction with MAdCAM-1

Murakami

Franco

et al. 2016

Stem Cells and Development

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“…On the other hand, blockade of α6 integrin enhanced the homing of human BM-derived HSPC and led to significantly improved engraftment [145]. Aside from the established role of the α 4 β 1 integrin receptor VCAM-1 in the homing of hematopoietic cells to the BM, the importance of MAdCAM-1 and its ligand, α 4 β 7 integrin, in the homing of BM-derived hematopoietic cells to both the spleen and the BM has been recently postulated [146]. …”

Section: Homingmentioning

confidence: 99%

The Ins and Outs of Hematopoietic Stem Cells: Studies to Improve Transplantation Outcomes

Marquez‐Curtis

Turner

Sridharan

et al. 2010

Stem Cell Rev and Rep

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Deciphering the mechanisms of hematopoietic stem/progenitor cell (HSPC) mobilization and homing is important for the development of strategies to enhance the efficacy of HSPC transplantation and achieve the full potential of HSPC-based cellular therapy. Investigation of these mechanisms has revealed interdependence among the various molecules, pathways and cellular components involved, and underscored the complex nature of these two processes. This review summarizes recent progress in identifying the specific factors implicated in HSPC mobilization and homing, with emphasis on our own work. Particularly, we will discuss our studies on stromal cell-derived factor-1 and its interaction with its receptor CXCR4, proteases (matrix metalloproteinases and carboxypeptidase M), complement proteins (C1q, C3a, C5a, membrane attack complex), sphingosine-1-phosphate, and pharmacologic agents such as the histone deacetylase inhibitor valproic acid and hyaluronic acid.

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“…The adhesion of stem cells and stromal cells is important for hematopoietic growth and development. For the functions of hematopoietic stromal cells, the expression of important CAMs, such as CD106 (VCAM-1), CD29 (integrin), and CD44, is helpful for stromal cells to exert their hematopoietic regulation functions [26], [27], [28]. CAMs can promote the homing of stromal cells after transplantation and play important roles in lymphocyte aggregation and immune response regulation.…”

Section: Discussionmentioning

confidence: 99%

Reconstruction of Hematopoietic Inductive Microenvironment after Transplantation of VCAM-1-Modified Human Umbilical Cord Blood Stromal Cells

Liu

Chen

et al. 2012

PLoS ONE

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The hematopoietic inductive microenvironment (HIM) is where hematopoietic stem/progenitor cells grow and develop. Hematopoietic stromal cells were the key components of the HIM. In our previous study, we had successfully cultured and isolated human cord blood–derived stromal cells (HUCBSCs) and demonstrated that they could secret hemopoietic growth factors such as GM-CSF, TPO, and SCF. However, it is still controversial whether HUCBSCs can be used for reconstruction of HIM. In this study, we first established a co-culture system of HUCBSCs and cord blood CD34 + cells and then determined that using HUCBSCs as the adherent layer had significantly more newly formed colonies of each hematopoietic lineage than the control group, indicating that HUCBSCs had the ability to promote the proliferation of hematopoietic stem cells/progenitor cells. Furthermore, the number of colonies was significantly higher in vascular cell adhesion molecule-1 (VCAM-1)-modified HUCBSCs, suggesting that the ability of HUCBSCs in promoting the proliferation of hematopoietic stem cells/progenitor cells was further enhanced after having been modified with VCAM-1. Next, HUCBSCs were infused into a radiation-damaged animal model, in which the recovery of hematopoiesis was observed. The results demonstrate that the transplanted HUCBSCs were “homed in” to bone marrow and played roles in promoting the recovery of irradiation-induced hematopoietic damage and repairing HIM. Compared with the control group, the HUCBSC group had significantly superior effectiveness in terms of the recovery time for hemogram and myelogram, CFU-F, CFU-GM, BFU-E, and CFU-Meg. Such differences were even more significant in VCAM-1-modified HUCBSCs group. We suggest that HUCBSCs are able to restore the functions of HIM and promote the recovery of radiation-induced hematopoietic damage. VCAM-1 plays an important role in supporting the repair of HIM damage.

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Role of MAdCAM-1 and Its Ligand on the Homing of Transplanted Hematopoietic Cells in Irradiated Mice

Abstract: We examined the expression of VCAM-1 and MAdCAM-1 after bone marrow transplantation (BMT

Cited by 10 publications

References 38 publications

Evidence that β7 Integrin Regulates Hematopoietic Stem Cell Homing and Engraftment Through Interaction with MAdCAM-1

Evidence that β7 Integrin Regulates Hematopoietic Stem Cell Homing and Engraftment Through Interaction with MAdCAM-1

The Ins and Outs of Hematopoietic Stem Cells: Studies to Improve Transplantation Outcomes

Reconstruction of Hematopoietic Inductive Microenvironment after Transplantation of VCAM-1-Modified Human Umbilical Cord Blood Stromal Cells

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