Mesenchymal stem cells promote engraftment of human umbilical cord blood–derived CD34+ cells in NOD/SCID mice

Noort, Willy A.; Kruisselbrink, Alwine B.; Anker, Pieternella S. in't; Kruger, Marjolein; Bezooijen, Rutger L. van; Paus, Roelf A de; Heemskerk, Mirjam H.M.; Löwik, Clemens W.G.M.; Falkenburg, J. H. F.; Willemze, R.; Fibbe, Willem E.

doi:10.1016/s0301-472x(02)00820-2

Cited by 448 publications

(337 citation statements)

References 34 publications

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“…The enhancing effect involved cells of myeloid, lymphoid and megakaryocytic lineages, with this finding showing that the engraftmentpromoting effect of MSCs was not lineage specific and it was particularly prominent when the dose of HSCs was low. 28,43 Altogether, these data suggest that co-infusion of MSCs could be a promising strategy to optimize the engraftment of UCB progenitors, especially in the presence of HLA disparities between the donor and the recipient, and have provided the rationale for testing the capacity of these cells to facilitate hematological recovery in human patients given allogeneic UCBT.…”

Section: Discussionmentioning

confidence: 99%

“…Ten study patients are alive, at a median follow-up of 28 months (range [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]; in the control group, 25 patients are alive with a median follow-up of 42 months (range 16-134). The Kaplan-Meier estimate of OS at 3 years is 63% (95% CI 43-97) and 64% (95% CI 48-79; P ¼ NS) in study patients and controls, respectively.…”

Section: Os Efs and Leukemia-free Survivalmentioning

confidence: 99%

“…Indeed, MSCs, which are multipotent cells capable of differentiation into several mesenchymal lineages, 21,22 possess peculiar properties of immunomodulation on all cells involved in the immune response. [23][24][25][26][27] Moreover, Noort et al 28 showed in a nonobese diabetic/SCID mouse model that co-transplantation of MSCs facilitated, both in BM and peripheral blood, UCB HSC engraftment, especially when low numbers of UCB-derived CD34 þ cells were infused.…”

Section: Introductionmentioning

confidence: 99%

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Co-infusion of ex vivo-expanded, parental MSCs prevents life-threatening acute GVHD, but does not reduce the risk of graft failure in pediatric patients undergoing allogeneic umbilical cord blood transplantation

Bernardo

Ball

Cometa

et al. 2010

Bone Marrow Transplant

160

120

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When compared with BMT, umbilical cord blood transplantation (UCBT) is associated with a lower rate of engraftment and delayed hematological/immunological recovery. This leads to increased risk of TRM in the early post transplantation period due to infection. Acute GVHD, although occurring less frequently in UCBT compared with BMT, is also significantly associated with increased rate of early TRM. BM MSCs are known to support normal in vivo hematopoiesis, and co-transplantation of MSCs has been shown to enhance engraftment of human cord blood hematopoietic cells in nonobese diabetic/SCID mice. In 13 children with hematological disorders (median age 2 years) undergoing UCBT, we cotransplanted paternal, HLA-disparate MSCs with the aim of improving hematological recovery and reducing rejection. We observed no differences in hematological recovery or rejection rates compared with 39 matched historical controls, most of whom received G-CSF after UCBT. However, the rate of grade III and IV acute GVHD was significantly decreased in the study cohort when compared with controls (P ¼ 0.05), thus resulting in reduced early TRM. Although these data do not support the use of MSCs in UCBT to support hematopoietic engraftment, they suggest that MSCs, possibly because of their immunosuppressive effect, may abrogate life-threatening acute GVHD and reduce early TRM.

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Section: Discussionmentioning

confidence: 99%

Section: Os Efs and Leukemia-free Survivalmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Co-infusion of ex vivo-expanded, parental MSCs prevents life-threatening acute GVHD, but does not reduce the risk of graft failure in pediatric patients undergoing allogeneic umbilical cord blood transplantation

Bernardo

Ball

Cometa

et al. 2010

Bone Marrow Transplant

160

120

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“…On the other hand, the MSC capability of facilitating the engraftment of transplanted HSC has been investigated in more detail [11,66]. In a non-human primate model of organ transplantation, MSC delayed the T cell-mediated rejection of skin allografts [12].…”

Section: Msc-mediated Immunological Effects In Vivomentioning

confidence: 99%

“…As a consequence, MSC hold promise not only for improving HSC engraftment upon allogeneic transplantation [11], but also for repairing damaged tissues. However, while MSC are naturally prone to differentiate into cells of mesodermal origin, their capacity of transdifferentiating in vivo is still debated and it is likely to be of limited biological relevance.…”

Section: Introductionmentioning

confidence: 99%

Immunoregulatory function of mesenchymal stem cells

2006

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Mesenchymal stem cells (MSC) are a rare subset of stem cells residing in the bone marrow where they closely interact with hematopoietic stem cells and support their growth and differentiation. MSC can differentiate into multiple mesenchymal and non‐mesenchymal lineages, providing a promising tool for tissue repair. In addition, MSC suppress many T cell, B cell and NK cell functions and may affect also dendritic cell activities. Due to their limited immunogenicity, MSC are poorly recognized by HLA‐incompatible hosts. Based on these unique properties, MSC are currently under investigation for their possible use to treat immuno‐mediated diseases. However, both their condition of immunoprivilege and their immunosuppressive function have recently been challenged when analyzed under particular experimental conditions. Thus, it is likely that MSC effects on the immune system may be deeply influenced not only by cell‐to‐cell interactions, but also by environmental factors shaping their phenotype and functions.

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Isolation and Expansion of Mesenchymal Stem Cells from Human Conjunctival Tissue

Nadri

Yazdani

2015

CP Stem Cell Biology

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Here we describe a simple protocol for the isolation and culture of mesenchymal stem cells (MSCs) from conjunctiva stromal tissue, with applications to stem cell biology and regenerative medicine. This protocol is based on an explant culture protocol for the adhesion and migration of MSCs from tissue biopsy in primary culture and expansion of the MSC population by passaging cells on the surface of plastic culture dishes. Conjunctiva mesenchymal stem cells (CJMSCs) are generally isolated from small biopsies of human conjunctival tissue. Epithelial sheets are carefully loosened and removed by enzyme treatment after 18 hr and placed in fresh medium supplemented with growth factors. When the cells migrating from tissue segments in primary cultures become nearly confluent, the culture is treated with trypsin. A purified population of CJMSCs that retain proliferation and differentiation potential for many passages can be obtained 2 weeks after the initiation of culture. © 2015 by John Wiley & Sons, Inc.

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Mesenchymal stem cells promote engraftment of human umbilical cord blood–derived CD34+ cells in NOD/SCID mice

Cited by 448 publications

References 34 publications

Co-infusion of ex vivo-expanded, parental MSCs prevents life-threatening acute GVHD, but does not reduce the risk of graft failure in pediatric patients undergoing allogeneic umbilical cord blood transplantation

Co-infusion of ex vivo-expanded, parental MSCs prevents life-threatening acute GVHD, but does not reduce the risk of graft failure in pediatric patients undergoing allogeneic umbilical cord blood transplantation

Immunoregulatory function of mesenchymal stem cells

Isolation and Expansion of Mesenchymal Stem Cells from Human Conjunctival Tissue

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