In utero hematopoietic stem cell transplantation: Rationale for continued work toward human application

2004 ◽  
Vol 191 (6) ◽  
pp. S162
Author(s):  
Scott Petersen ◽  
Mariya Gendelman ◽  
Richard Jones ◽  
Allen Chen ◽  
Karin Blakemore
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
In Utero ◽  
Hematopoietic Stem

scholarly journals In utero fetal liver hematopoietic stem cell transplantation: is there a role for alloreactive T lymphocytes?

Blood ◽  
2000 ◽  
Vol 96 (4) ◽  
pp. 1608-1609
Author(s):  
Maria Concetta Renda ◽  
Emanuela Fecarotta ◽  
Aurelio Maggio ◽  
Francesco Dieli ◽  
Guido Sireci ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Lymphocytes ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Fetal Liver ◽  
In Utero ◽  
Hematopoietic Stem

scholarly journals In utero Hematopoietic Stem Cell Transplantation in Canines: Exploring the Gestational Age Window of Opportunity to Maximize Engraftment

2013 ◽  
Vol 33 (2) ◽  
pp. 116-121 ◽  
Author(s):  
Scott M. Petersen ◽  
Mariya Gendelman ◽  
Kathleen M. Murphy ◽  
Michael Torbenson ◽  
Richard J. Jones ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Gestational Age ◽  
In Utero ◽  
Window Of Opportunity ◽  
Hematopoietic Stem

scholarly journals In utero fetal liver hematopoietic stem cell transplantation: is there a role for alloreactive T lymphocytes?

Blood ◽  
2000 ◽  
Vol 96 (4) ◽  
pp. 1608-1609 ◽  
Author(s):  
Maria Concetta Renda ◽  
Emanuela Fecarotta ◽  
Aurelio Maggio ◽  
Francesco Dieli ◽  
Guido Sireci ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Lymphocytes ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Fetal Liver ◽  
In Utero ◽  
Hematopoietic Stem

Tolerance induction and microglial engraftment after fetal therapy without conditioning in mice with mucopolysaccharidosis type VII

2020 ◽  
Vol 12 (532) ◽  
pp. eaay8980 ◽  
Author(s):  
Quoc-Hung Nguyen ◽  
Russell G. Witt ◽  
Bowen Wang ◽  
Carlo Eikani ◽  
Jeremy Shea ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
In Utero ◽  
Mucopolysaccharidosis Type ◽  
Fetal Therapy ◽  
Hematopoietic Stem ◽  
Enzyme Replacement

Mucopolysaccharidosis type VII (MPS7) is a lysosomal storage disorder (LSD) resulting from mutations in the β-glucuronidase gene, leading to multiorgan dysfunction and fetal demise. While postnatal enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation have resulted in some phenotypic improvements, prenatal treatment might take advantage of a unique developmental window to penetrate the blood-brain barrier or induce tolerance to the missing protein, addressing two important shortcomings of postnatal therapy for multiple LSDs. We performed in utero ERT (IUERT) at E14.5 in MPS7 mice and improved survival of affected mice to birth. IUERT penetrated brain microglia, whereas postnatal administration did not, and neurological testing (after IUERT plus postnatal administration) showed decreased microglial inflammation and improved grip strength in treated mice. IUERT prevented antienzyme antibody development even after multiple repeated postnatal challenges. To test a more durable treatment strategy, we performed in utero hematopoietic stem cell transplantation (IUHCT) using congenic CX3C chemokine receptor 1–green fluorescent protein (CX3CR1-GFP) mice as donors, such that donor-derived microglia are identified by GFP expression. In wild-type recipients, hematopoietic chimerism resulted in microglial engraftment throughout the brain without irradiation or conditioning; the transcriptomes of donor and host microglia were similar. IUHCT in MPS7 mice enabled cross-correction of liver Kupffer cells and improved phenotype in multiple tissues. Engrafted microglia were seen in chimeric mice, with decreased inflammation near donor microglia. These results suggest that fetal therapy with IUERT and/or IUHCT could overcome the shortcomings of current treatment strategies to improve phenotype in MPS7 and other LSDs.

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