HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Noia, G. Articles by Mancuso, S. Search for Related Content PubMed PubMed Citation Articles by Noia, G. Articles by Mancuso, S.

A Novel Route of Transplantation of Human Cord Blood Stem Cells in Preimmune Fetal Sheep: The Intracelomic Cavity

^a Department of Obstetrics and Gynecology,
^b Department of Hematology,
^c Department of Anatomy, Catholic University of the Sacred Heart, Rome, Italy;
^d Zootecnic Experimental Institute, Monterotondo, Italy;
^e Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Hospital, Rome, Italy

Key Words. In utero transplantation • Intracelomic route

Giuseppe Noia, M.D., Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Largo Agostino Gemelli 8, 00168 Rome, Italy. Telephone: 39-06-30154979; Fax: 39-06-3051160; e-mail: pi.noia{at}tin.it

The intracelomic route for in utero hematopoietic stem cell transplantation was evaluated in preimmune fetal sheep and the engraftment characteristics were defined. Twelve twin ovine fetuses (gestational age: 40–45 days) received intracelomic transplants of human CD3-depleted (50 x 10⁶ per lamb) or CD34-selected (1–2 x 10⁵ per lamb) cord blood hematopoietic stem cells. Engraftment was evaluated from cell suspensions of the liver, spleen, bone marrow, and thymus by flow cytometry, cloning assays, and polymerase chain reaction (PCR) analyses of human ß2-microglobulin. Four fetuses (33%) aborted shortly after intracelomic transplantation and were not evaluable for engraftment. Engraftment was detected in four fetuses obtained from cesarean delivery on day 70 after transplantation of CD3-depleted cord blood cells. The degrees of engraftment in these four fetuses ranged from 6%-22% in the different organs (as revealed by antigenic analysis of human CD45 with flow cytometry). Three fetuses obtained after cesarean section at 102 (no. 435184) and 105 (no. 915293, no. 037568) days and one fetus delivered at term that received CD34-selected cord blood cells had human engraftment with 10%, 32%, 20%, and 10% CD45⁺ cells in bone marrow, respectively. In six of eight fetuses evaluable for human engraftment, chimerism was confirmed by PCR analysis for human ß2-microglobulin, which also identified human cells in brain, spinal cord, heart, lung, and skeletal muscle. This preliminary study indicates that intracelomic transplantation of human hematopoietic stem cells in fetal lambs is feasible and effective in terms of hematopoietic engraftment.