IN UTERO HAEMATOPOIETIC STEM CELL TRANSPLANTATION (IUHSCT)

Abstract

<p class="MsoNormal" style="margin: 0cm 0cm 0pt; line-height: 200%; text-align: justify;"><span style="color: black; mso-ansi-language: EN-GB;" lang="EN-GB"><span style="font-size: small;"><span style="font-family: Times New Roman;">In utero haematopoietic stem cell transplantation (IUHSCT) is a non-myeloablative approach for the prenatal treatment of genetic disorders. However, in target disorders, where there is not a selective advantage for donor cells, a useful donor-cell<span style="mso-spacerun: yes;"> </span>chimerism<span style="mso-spacerun: yes;"> </span>has not been achieved<span style="mso-spacerun: yes;"> </span></span></span></span></p><p class="MsoNormal" style="margin: 0cm 0cm 0pt; line-height: 200%; text-align: justify;"><span style="color: black; mso-ansi-language: EN-GB;" lang="EN-GB"><span style="font-size: small;"><span style="font-family: Times New Roman;">There are three<span style="mso-spacerun: yes;"> </span>possible<span style="mso-spacerun: yes;"> </span>barriers<span style="mso-spacerun: yes;"> </span>to engraftment following IUHSCT :<span style="mso-spacerun: yes;"> </span>limited space in the fetus due to host-cell competition; the large number of donor cells needed, and the immunological asset of recipient .</span></span></span></p><p class="MsoNormal" style="margin: 0cm 0cm 0pt; line-height: 200%; text-align: justify; mso-layout-grid-align: none;"><span style="color: black; mso-ansi-language: EN-GB;" lang="EN-GB"><span style="font-size: small;"><span style="font-family: Times New Roman;">Animal models have shown different levels of resistance to IUHSCT engraftment.<span style="mso-spacerun: yes;"> </span>In primate, goat, rat and mouse<span style="mso-spacerun: yes;"> </span>the levels of engraftment that has been achieved were low and not<span style="mso-spacerun: yes;"> </span>therapeutic.</span></span></span></p><p class="MsoNormal" style="margin: 0cm 0cm 0pt; line-height: 200%; text-align: justify; mso-layout-grid-align: none;"><span style="color: black; mso-ansi-language: EN-GB;" lang="EN-GB"><span style="font-size: small;"><span style="font-family: Times New Roman;">Among 46 cases of<span style="mso-spacerun: yes;"> </span>IUHSCT reported in humans, successful engraftment<span style="mso-spacerun: yes;"> </span>was obtained only in cases of<span style="mso-spacerun: yes;"> </span>X-SCID. Useful levels of chimerism has not been achieved in non-immunodeficiency diseases, and<span style="mso-spacerun: yes;"> </span>a detectable engrafment , was<span style="mso-spacerun: yes;"> </span>reported only in one case<span style="mso-spacerun: yes;"> </span>of<span style="mso-spacerun: yes;"> </span>ß-thalassemia transplanted at 12 weeks of gestation<span style="mso-spacerun: yes;"> </span>by fetal liver cells<span style="mso-spacerun: yes;"> </span></span></span></span></p><p class="MsoNormal" style="margin: 0cm 0cm 0pt; line-height: 200%; text-align: justify;"><span style="font-size: small;"><span style="color: black; mso-ansi-language: EN-GB;" lang="EN-GB"><span style="font-family: Times New Roman;">In one </span></span><span style="color: black; font-family: Symbol; mso-ansi-language: EN-GB; mso-ascii-font-family: 'Times New Roman'; mso-hansi-font-family: 'Times New Roman'; mso-char-type: symbol; mso-symbol-font-family: Symbol;" lang="EN-GB"><span style="mso-char-type: symbol; mso-symbol-font-family: Symbol;">a</span></span><span style="color: black; mso-ansi-language: EN-GB;" lang="EN-GB"><span style="font-family: Times New Roman;">-thalassemia case, where </span></span><span style="color: black; font-family: Symbol; mso-ansi-language: EN-GB; mso-ascii-font-family: 'Times New Roman'; mso-hansi-font-family: 'Times New Roman'; mso-char-type: symbol; mso-symbol-font-family: Symbol;" lang="EN-GB"><span style="mso-char-type: symbol; mso-symbol-font-family: Symbol;">a</span></span><span style="color: black; mso-ansi-language: EN-GB;" lang="EN-GB"><span style="font-family: Times New Roman;">-globin-dependent hemoglobin production and anemia are present during fetal period, microchimerism<span style="mso-spacerun: yes;"> </span>and tolerance were suggested. </span></span></span></p><p class="MsoNormal" style="margin: 0cm 0cm 0pt; line-height: 200%; text-align: justify;"><span style="color: black; mso-ansi-language: EN-GB;" lang="EN-GB"><span style="font-size: small;"><span style="font-family: Times New Roman;">To overcome the IUHSCT engraftment barriers , it is necessary to develop strategies to improve the competitive capacity of donor cells and<span style="mso-spacerun: yes;"> </span>to define the gestational age of the possible immunological “window of opportunity” in the human fetus. </span></span></span></p><p class="MsoNormal" style="margin: 0cm 0cm 0pt; line-height: 200%; text-align: justify;"><span style="color: black; mso-ansi-language: EN-GB;" lang="EN-GB"><span style="font-size: small;"><span style="font-family: Times New Roman;">In utero haematopoietic stem cell transplantation (IUHSCT) is a non-myeloablative promising approach for the prenatal treatment of a variety of genetic disorders and<span style="mso-spacerun: yes;"> </span>could be an alternative<span style="mso-spacerun: yes;"> </span>option to therapeutical abortion in some congenital diseases like haematological hereditary<span style="mso-spacerun: yes;"> </span>syndromes. </span></span></span></p>

Keywords

• Thalassemia, Hemoglobin Disorders, Hemopietic Stem Cell Transplantation, Pregnacy, In utero