10779/crick.11549568.v1
Stavros P Loukogeorgakis
Stavros P
Loukogeorgakis
Panicos Shangaris
Panicos
Shangaris
Enrica Bertin
Enrica
Bertin
Chiara Franzin
Chiara
Franzin
Martina Piccoli
Martina
Piccoli
Michela Pozzobon
Michela
Pozzobon
Sindhu Subramaniam
Sindhu
Subramaniam
Alfonso Tedeschi
Alfonso
Tedeschi
Aimee G Kim
Aimee G
Kim
Haiying Li
Haiying
Li
Camila G Fachin
Camila G
Fachin
Andre IBS Dias
Andre IBS
Dias
John D Stratigis
John D
Stratigis
Nicholas J Ahn
Nicholas J
Ahn
Adrian J Thrasher
Adrian J
Thrasher
Paola Bonfanti
Paola
Bonfanti
William H Peranteau
William H
Peranteau
Anna L David
Anna L
David
Alan W Flake
Alan W
Flake
Paolo De Coppi
Paolo
De Coppi
In utero transplantation of expanded autologous amniotic fluid stem cells results in long-term hematopoietic engraftment.
The Francis Crick Institute
2020
Fetal stem cells
autologous stem cell transplantation
cell culture
hematopoiesis
transplantation tolerance
Autologous stem cell transplantation
Cell culture
Hematopoiesis
Transplantation tolerance
Bonfanti - sec
06 Biological Sciences
10 Technology
11 Medical and Health Sciences
Immunology
2020-01-08 16:58:32
Journal contribution
https://crick.figshare.com/articles/journal_contribution/In_utero_transplantation_of_expanded_autologous_amniotic_fluid_stem_cells_results_in_long-term_hematopoietic_engraftment_/11549568
In utero transplantation (IUT) of hematopoietic stem cells (HSC) has been proposed as a strategy for the prenatal treatment of congenital hematological diseases. However, levels of long-term hematopoietic engraftment achieved in experimental IUT to date are sub-therapeutic, likely due to host fetal HSC out-competing their bone-marrow (BM) derived donor equivalents for space in the hematopoietic compartment. In the present study we demonstrate that amniotic fluid stem cells (AFSC; c-Kit+/Lin-) have hematopoietic characteristics and, thanks to their fetal origin, favourable proliferation kinetics in vitro and in vivo, which are maintained when the cells are expanded. IUT of autologous/congenic freshly-isolated or cultured AFSC resulted in stable mutli-lineage hematopoietic engraftment, far higher to that achieved with BM-HSC. Intravascular IUT of allogenic AFSC was not successful as recently reported after intraperitoneal IUT. Herein we demonstrated that this likely due to a failure of timely homing of donor cells to the host fetal thymus resulted in lack of tolerance induction and rejection. This study reveals that intravascular IUT leads to a remarkable hematopoietic engraftment of AFSC in the setting of autologous/congenic IUT, and confirms the requirement for induction of central tolerance for allogenic IUT to be successful. Autologous, gene engineered and in-vitro expanded AFSC could be used as a stem cell/gene therapy platform for the in utero treatment of inherited disorders of hematopoiesis. SIGNIFICANCE STATEMENT: Amniotic fluid stem cells can be expanded without losing their hematopoietic characteristics In utero transplantation of allogenic AFSC results in adaptive immune response and donor cell rejection, due to failure of timely homing of donor cells to the host fetal thymus and lack of central tolerance induction. Autologous/congenic amniotic fluid stem cells can be transplanted in utero and result in stable, multi-lineage, long-term hematopoietic engraftment that is significantly higher to that achieved with bone marrow-derived cells and could be therapeutic in many inherited disorders of hematopoiesis. © AlphaMed Press 2019.