Chimerism and tolerance post-in utero transplantation with embryonic stem cells

Mohamed E. Moustafa, Anand S. Srivastava, Elena Nedelcu, Jody Donahue, Ivelina Gueorguieva, Steve S. Shenouda, Boris Minev, Ewa Carrier

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background. Clinical application of in utero transplantation (IUT) in human fetuses with intact immune systems resulted in a very low level of donor chimerism. In this study, we examined whether the fetal immune system early in the second trimester of pregnancy (13.5 dpc) can initiate immune tolerance for major histocompatibility complex (MHC)-mismatched embryonic stem (ES) cells. We also examined whether immune tolerance mechanisms respond differently to ontogenetically different stem cells. Methods. MHC-mismatched ES, fetal liver (FL), and bone-marrow (BM) cells (H-2kb) at 1 × 109 cells/kg fetal body weight were injected intraperitoneally into 13.5 dpc BALB/c fetuses (H-2Kd). Peripheral chimerism was determined in blood by flow cytometry (sensitivity≤0.1%) at monthly intervals. Donor-specific immune responses were determined by cytotoxic lymphocyte (CTL) assay, mixed lymphocyte reaction, and T helper (Th)1 and Th2 cytokine assays. Chimeric mice at the age of 9 months received postnatal boosts (PB) with minimal conditioning of 200 cGy by intravenous injection of 1 × 109 of the corresponding cells/kg body weight. Results. After IUT with ES, FL, or BM cells, the level of peripheral chimerism within the first 9 months of life was 0% to 0.4%. PB with 1 × 109/kg of corresponding cells resulted in a decrease in the peripheral chimerism to 0% within 2 weeks of PB. CTL and cytokine assays before and after PB demonstrated a shift toward immunity. Conclusions. Immunologic tolerance was not achieved after IUT of murine fetuses at 13.5 dpc with MHC-mismatched ES cells, and only a low level chimerism was achieved.

Original languageEnglish (US)
Pages (from-to)1274-1282
Number of pages9
JournalTransplantation
Volume78
Issue number9
DOIs
StatePublished - Nov 15 2004

Fingerprint

Chimerism
Embryonic Stem Cells
Transplantation
Major Histocompatibility Complex
Immune Tolerance
Fetus
Bone Marrow Cells
Immune System
Lymphocytes
Cytokines
Fetal Weight
Mixed Lymphocyte Culture Test
Liver
Second Pregnancy Trimester
Intravenous Injections
Immunity
Flow Cytometry
Stem Cells
Body Weight

Keywords

  • Embryonic stem cells
  • Immunity
  • In utero transplantation
  • Tolerance
  • Transplantation

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Moustafa, M. E., Srivastava, A. S., Nedelcu, E., Donahue, J., Gueorguieva, I., Shenouda, S. S., ... Carrier, E. (2004). Chimerism and tolerance post-in utero transplantation with embryonic stem cells. Transplantation, 78(9), 1274-1282. https://doi.org/10.1097/01.TP.0000137267.17002.B5

Chimerism and tolerance post-in utero transplantation with embryonic stem cells. / Moustafa, Mohamed E.; Srivastava, Anand S.; Nedelcu, Elena; Donahue, Jody; Gueorguieva, Ivelina; Shenouda, Steve S.; Minev, Boris; Carrier, Ewa.

In: Transplantation, Vol. 78, No. 9, 15.11.2004, p. 1274-1282.

Research output: Contribution to journalArticle

Moustafa, ME, Srivastava, AS, Nedelcu, E, Donahue, J, Gueorguieva, I, Shenouda, SS, Minev, B & Carrier, E 2004, 'Chimerism and tolerance post-in utero transplantation with embryonic stem cells', Transplantation, vol. 78, no. 9, pp. 1274-1282. https://doi.org/10.1097/01.TP.0000137267.17002.B5
Moustafa ME, Srivastava AS, Nedelcu E, Donahue J, Gueorguieva I, Shenouda SS et al. Chimerism and tolerance post-in utero transplantation with embryonic stem cells. Transplantation. 2004 Nov 15;78(9):1274-1282. https://doi.org/10.1097/01.TP.0000137267.17002.B5
Moustafa, Mohamed E. ; Srivastava, Anand S. ; Nedelcu, Elena ; Donahue, Jody ; Gueorguieva, Ivelina ; Shenouda, Steve S. ; Minev, Boris ; Carrier, Ewa. / Chimerism and tolerance post-in utero transplantation with embryonic stem cells. In: Transplantation. 2004 ; Vol. 78, No. 9. pp. 1274-1282.
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abstract = "Background. Clinical application of in utero transplantation (IUT) in human fetuses with intact immune systems resulted in a very low level of donor chimerism. In this study, we examined whether the fetal immune system early in the second trimester of pregnancy (13.5 dpc) can initiate immune tolerance for major histocompatibility complex (MHC)-mismatched embryonic stem (ES) cells. We also examined whether immune tolerance mechanisms respond differently to ontogenetically different stem cells. Methods. MHC-mismatched ES, fetal liver (FL), and bone-marrow (BM) cells (H-2kb) at 1 × 109 cells/kg fetal body weight were injected intraperitoneally into 13.5 dpc BALB/c fetuses (H-2Kd). Peripheral chimerism was determined in blood by flow cytometry (sensitivity≤0.1{\%}) at monthly intervals. Donor-specific immune responses were determined by cytotoxic lymphocyte (CTL) assay, mixed lymphocyte reaction, and T helper (Th)1 and Th2 cytokine assays. Chimeric mice at the age of 9 months received postnatal boosts (PB) with minimal conditioning of 200 cGy by intravenous injection of 1 × 109 of the corresponding cells/kg body weight. Results. After IUT with ES, FL, or BM cells, the level of peripheral chimerism within the first 9 months of life was 0{\%} to 0.4{\%}. PB with 1 × 109/kg of corresponding cells resulted in a decrease in the peripheral chimerism to 0{\%} within 2 weeks of PB. CTL and cytokine assays before and after PB demonstrated a shift toward immunity. Conclusions. Immunologic tolerance was not achieved after IUT of murine fetuses at 13.5 dpc with MHC-mismatched ES cells, and only a low level chimerism was achieved.",
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AU - Srivastava, Anand S.

AU - Nedelcu, Elena

AU - Donahue, Jody

AU - Gueorguieva, Ivelina

AU - Shenouda, Steve S.

AU - Minev, Boris

AU - Carrier, Ewa

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N2 - Background. Clinical application of in utero transplantation (IUT) in human fetuses with intact immune systems resulted in a very low level of donor chimerism. In this study, we examined whether the fetal immune system early in the second trimester of pregnancy (13.5 dpc) can initiate immune tolerance for major histocompatibility complex (MHC)-mismatched embryonic stem (ES) cells. We also examined whether immune tolerance mechanisms respond differently to ontogenetically different stem cells. Methods. MHC-mismatched ES, fetal liver (FL), and bone-marrow (BM) cells (H-2kb) at 1 × 109 cells/kg fetal body weight were injected intraperitoneally into 13.5 dpc BALB/c fetuses (H-2Kd). Peripheral chimerism was determined in blood by flow cytometry (sensitivity≤0.1%) at monthly intervals. Donor-specific immune responses were determined by cytotoxic lymphocyte (CTL) assay, mixed lymphocyte reaction, and T helper (Th)1 and Th2 cytokine assays. Chimeric mice at the age of 9 months received postnatal boosts (PB) with minimal conditioning of 200 cGy by intravenous injection of 1 × 109 of the corresponding cells/kg body weight. Results. After IUT with ES, FL, or BM cells, the level of peripheral chimerism within the first 9 months of life was 0% to 0.4%. PB with 1 × 109/kg of corresponding cells resulted in a decrease in the peripheral chimerism to 0% within 2 weeks of PB. CTL and cytokine assays before and after PB demonstrated a shift toward immunity. Conclusions. Immunologic tolerance was not achieved after IUT of murine fetuses at 13.5 dpc with MHC-mismatched ES cells, and only a low level chimerism was achieved.

AB - Background. Clinical application of in utero transplantation (IUT) in human fetuses with intact immune systems resulted in a very low level of donor chimerism. In this study, we examined whether the fetal immune system early in the second trimester of pregnancy (13.5 dpc) can initiate immune tolerance for major histocompatibility complex (MHC)-mismatched embryonic stem (ES) cells. We also examined whether immune tolerance mechanisms respond differently to ontogenetically different stem cells. Methods. MHC-mismatched ES, fetal liver (FL), and bone-marrow (BM) cells (H-2kb) at 1 × 109 cells/kg fetal body weight were injected intraperitoneally into 13.5 dpc BALB/c fetuses (H-2Kd). Peripheral chimerism was determined in blood by flow cytometry (sensitivity≤0.1%) at monthly intervals. Donor-specific immune responses were determined by cytotoxic lymphocyte (CTL) assay, mixed lymphocyte reaction, and T helper (Th)1 and Th2 cytokine assays. Chimeric mice at the age of 9 months received postnatal boosts (PB) with minimal conditioning of 200 cGy by intravenous injection of 1 × 109 of the corresponding cells/kg body weight. Results. After IUT with ES, FL, or BM cells, the level of peripheral chimerism within the first 9 months of life was 0% to 0.4%. PB with 1 × 109/kg of corresponding cells resulted in a decrease in the peripheral chimerism to 0% within 2 weeks of PB. CTL and cytokine assays before and after PB demonstrated a shift toward immunity. Conclusions. Immunologic tolerance was not achieved after IUT of murine fetuses at 13.5 dpc with MHC-mismatched ES cells, and only a low level chimerism was achieved.

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