In utero hematopoietic cell transplantation—recent progress and the potential for clinical application

Vrecenak, Jesse D.; Flake, Alan W.

doi:10.1016/j.jcyt.2013.01.003

Cited by 39 publications

(39 citation statements)

References 98 publications

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“…IUT has been proposed as a novel approach for the treatment of inherited haematological disorders (including thalassaemia and sickle cell disease) before birth [29]. Clinical translation to date has been limited by competitive and immunological barriers associated with IUT of adult bonemarrow-derived haematopoietic stem cells (BMHSCs) [30]. The use of AFSCs for IUT could address many of these limitations.…”

Section: Haematopoietic Systemmentioning

confidence: 99%

Stem cells from amniotic fluid – Potential for regenerative medicine

Loukogeorgakis

Coppi

2016

Best Practice & Research Clinical Obstetrics & Gynaecol

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Section: Haematopoietic Systemmentioning

confidence: 99%

Stem cells from amniotic fluid – Potential for regenerative medicine

Loukogeorgakis

Coppi

2016

Best Practice & Research Clinical Obstetrics & Gynaecol

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“…1 The clinical promise of IUHCT has not yet been realized because of significant barriers to donor cell engraftment within the fetal environment. 2 In the murine model, the primary barriers include a formidable competitive barrier from the healthy, nonmyeloablated host hematopoietic compartment and the maternal immune response.…”

Section: Introductionmentioning

confidence: 99%

Stable long-term mixed chimerism achieved in a canine model of allogeneic in utero hematopoietic cell transplantation

Vrecenak¹,

Pearson²,

Santore³

et al. 2014

Blood

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Key Points• Optimization of IUHCT in a preclinical canine model yields stable long-term donor engraftment.• Clinically significant levels of chimerism can be achieved without conditioning, immunosuppression, or graft-versushost disease.Evidence supporting the efficacy of in utero hematopoietic cell transplantation (IUHCT) in a valid large animal model is needed prior to clinical application. The objective of this study was to establish clinically relevant levels of hematopoietic chimerism in a canine model of maternal-to-fetal IUHCT. We first assessed immune and hematopoietic ontogeny relevant to IUHCT in the canine model and identified 40 days' gestation (term 63 days) as a time point at the initiation of thymic selection, and prior to bone marrow hematopoiesis, that might be optimal for IUHCT. We next determined that intravascular administration of donor cells via intracardiac injection was far more efficient and resulted in much higher levels of donor cell engraftment than intraperitoneal injection. By applying these findings, we achieved stable long-term multilineage engraftment in 21 of 24 surviving recipients with an average level of initial chimerism of 11.7% (range 3% to 39%) without conditioning or evidence of graft-versus-host disease. Donor cell chimerism remained stable for up to 2 years and was associated with donor-specific tolerance for renal transplantation. The levels of donor cell chimerism achieved in this study would be therapeutic for many hematopoietic disorders and are supportive of a clinical trial

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“…Unfortunately, these findings did not translate into similar results in clinical studies. Successful engraftment following IUHCT in humans has been limited to circumstances of immunodeficiency and those in which a donor cell selective advantage exists (Flake et al, 1996; Wengler et al, 1996; Gil et al, 1999; Bartolome et al, 2002; Pirovano et al, 2004; Touraine et al, 2004; Muench, 2005; De Santis et al, 2011). These discouraging results highlighted the need for a more in depth study of the events following IUHCT including the induction of donor specific tolerance.…”

Section: Iuhct and Allogeneic Engraftment: From Micro To Macrochimerimentioning

confidence: 99%

In utero hematopoietic cell transplantation: induction of donor specific immune tolerance and postnatal transplants

Peranteau

2014

Front. Pharmacol.

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In utero hematopoietic cell transplantation (IUHCT) is a non-myeloablative non-immunosuppressive transplant approach that allows for donor cell engraftment across immunologic barriers. Successful engraftment is associated with donor-specific tolerance. IUHCT has the potential to treat a large number of congenital hematologic, immunologic, and genetic diseases either by achieving high enough engraftment levels following a single IUHCT or by inducing donor specific tolerance to allow for non-toxic same-donor postnatal transplants. This review evaluates donor specific tolerance induction achieved by IUHCT. Specifically it addresses the need to achieve threshold levels of donor cell engraftment following IUHCT to consistently obtain immunologic tolerance. The mechanisms of tolerance induction including partial deletion of donor reactive host T cells by direct and indirect antigen presentation and the role of regulatory T cells in maintaining tolerance are reviewed. Finally, this review highlights the promising clinical potential of in utero tolerance induction to provide a platform on which postnatal cellular and organ transplants can be performed without myeloablative or immunosuppressive conditioning.

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In utero hematopoietic cell transplantation—recent progress and the potential for clinical application

Cited by 39 publications

References 98 publications

Stem cells from amniotic fluid – Potential for regenerative medicine

Stem cells from amniotic fluid – Potential for regenerative medicine

Stable long-term mixed chimerism achieved in a canine model of allogeneic in utero hematopoietic cell transplantation

In utero hematopoietic cell transplantation: induction of donor specific immune tolerance and postnatal transplants

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