Abstract
Recent advances in stem cell biology, prenatal diagnosis, and fetal surgery have transformed our ability to use in utero stem cell transplantation to cure congenital anomalies. With the recent discovery of inducible pluripotent stem (iPS) cells [1], new opportunities are available to generate patient-matched iPS cells for specific diseases. Advances in prenatal imaging and molecular diagnostics allow us to accurately diagnose congenital hematologic diseases as early as 10–12 weeks of gestation [2]. Furthermore, high-resolution ultrasonography has made it technically feasible to deliver stem cells in the early gestation fetus. Fetal intervention in patients has expanded since its first description in 1982 [3] and is used to treat anatomic anomalies with both conventional and minimally invasive techniques [4]. The improved understanding of stem cell biology, the ability to diagnose congenital diseases that are amenable to prenatal therapy, and the technical capability to deliver cells safely in utero have brought renewed interest and excitement for the promise of prenatal stem cell therapy.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–76.
Flake AW, Zanjani ED. In utero hematopoietic stem cell transplantation: ontogenic opportunities and biologic barriers. Blood. 1999;94:2179–91.
Harrison MR, Golbus MS, Filly RA, et al. Fetal surgery for congenital hydronephrosis. N Engl J Med. 1982;306:591–3.
Sydorak RM, Nijagal A, Albanese CT. Endoscopic techniques in fetal surgery. Yonsei Med J. 2001;42:695–710.
Morrison SJ, Uchida N, Weissman IL. The biology of hematopoietic stem cells. Annu Rev Cell Dev Biol. 1995;11:35–71.
Johnson FL, Look AT, Gockerman J, Ruggiero MR, Dalla-Pozza L, Billings 3rd FT. Bone-marrow transplantation in a patient with sickle-cell anemia. N Engl J Med. 1984;311:780–3.
Kamani N, August CS, Douglas SD, Burkey E, Etzioni A, Lischner HW. Bone marrow transplantation in chronic granulomatous disease. J Pediatr. 1984;105:42–6.
Lucarelli G, Galimberti M, Polchi P, et al. Bone marrow transplantation in patients with thalassemia. N Engl J Med. 1990;322:417–21.
Parkman R. The application of bone marrow transplantation to the treatment of genetic diseases. Science. 1986;232:1373–8.
Santore MT, Roybal JL, Flake AW. Prenatal stem cell transplantation and gene therapy. Clin Perinatol. 2009;36:451–71, xi.
Elder M, Golbus MS, Cowan MJ. Ontogeny of T- and B-cell immunity. In: Edwards RG, editor. Fetal tissue transplants in medicine. Cambridge: University Press; 1992. p. 97–128.
Medvinsky A, Dzierzak E. Definitive hematopoiesis is autonomously initiated by the AGM region. Cell. 1996;86:897–906.
Palmer E. Negative selection – clearing out the bad apples from the T-cell repertoire. Nat Rev Immunol. 2003;3:383–91.
Ashizuka S, Peranteau WH, Hayashi S, Flake AW. Busulfan-conditioned bone marrow transplantation results in high-level allogeneic chimerism in mice made tolerant by in utero hematopoietic cell transplantation. Exp Hematol. 2006;34:359–68.
Hayashi S, Peranteau WH, Shaaban AF, Flake AW. Complete allogeneic hematopoietic chimerism achieved by a combined strategy of in utero hematopoietic stem cell transplantation and postnatal donor lymphocyte infusion. Blood. 2002;100:804–12.
Peranteau WH, Hayashi S, Hsieh M, Shaaban AF, Flake AW. High-level allogeneic chimerism achieved by prenatal tolerance induction and postnatal nonmyeloablative bone marrow transplantation. Blood. 2002;100:2225–34.
Owen RD. Immunogenetic consequences of vascular anastomoses between bovine twins. Science. 1945;102:400–1.
Thomsen M, Hansen HE, Dickmeiss E. MLC and CML studies in the family of a pair of HLA haploidentical chimeric twins. Scand J Immunol. 1977;6:523–8.
Picus J, Aldrich WR, Letvin NL. A naturally occurring bone-marrow-chimeric primate. I. Integrity of its immune system. Transplantation. 1985;39:297–303.
Picus J, Holley K, Aldrich WR, Griffin JD, Letvin NL. A naturally occurring bone marrow-chimeric primate. II. Environment dictates restriction on cytolytic T lymphocyte-target cell interactions. J Exp Med. 1985;162:2035–52.
Andrassy J, Kusaka S, Jankowska-Gan E, et al. Tolerance to noninherited maternal MHC antigens in mice. J Immunol. 2003;171:5554–61.
Burlingham WJ, Grailer AP, Heisey DM, et al. The effect of tolerance to noninherited maternal HLA antigens on the survival of renal transplants from sibling donors. N Engl J Med. 1998;339:1657–64.
van Rood JJ, Loberiza Jr FR, Zhang MJ, et al. Effect of tolerance to noninherited maternal antigens on the occurrence of graft-versus-host disease after bone marrow transplantation from a parent or an HLA-haploidentical sibling. Blood. 2002;99:1572–7.
Mold JE, Michaelsson J, Burt TD, et al. Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero. Science. 2008;322:1562–5.
Sabatino DE, Mackenzie TC, Peranteau W, et al. Persistent expression of hF.IX After tolerance induction by in utero or neonatal administration of AAV-1-F.IX in hemophilia B mice. Mol Ther. 2007;15:1677–85.
Gouw SC, van den Berg HM. The multifactorial etiology of inhibitor development in hemophilia: genetics and environment. Semin Thromb Hemost. 2009;35:723–34.
Billingham RE, Brent L, Medawar PB. Actively acquired tolerance of foreign cells. Nature. 1953;172:603–6.
Blazar BR, Taylor PA, Vallera DA. In utero transfer of adult bone marrow cells into recipients with severe combined immunodeficiency disorder yields lymphoid progeny with T- and B-cell functional capabilities. Blood. 1995;86:4353–66.
Blazar BR, Taylor PA, Vallera DA. Adult bone marrow-derived pluripotent hematopoietic stem cells are engraftable when transferred in utero into moderately anemic fetal recipients. Blood. 1995;85:833–41.
Carrier E, Gilpin E, Lee TH, Busch MP, Zanetti M. Microchimerism does not induce tolerance after in utero transplantation and may lead to the development of alloreactivity. J Lab Clin Med. 2000;136:224–35.
Kim HB, Shaaban AF, Milner R, Fichter C, Flake AW. In utero bone marrow transplantation induces donor-specific tolerance by a combination of clonal deletion and clonal anergy. J Pediatr Surg. 1999;34:726–9; discussion 9–30.
Kim HB, Shaaban AF, Yang EY, Liechty KW, Flake AW. Microchimerism and tolerance after in utero bone marrow transplantation in mice. J Surg Res. 1998;77:1–5.
Pallavicini MG, Flake AW, Madden D, et al. Hematopoietic chimerism in rodents transplanted in utero with fetal human hematopoietic cells. Transplant Proc. 1992;24:542–3.
Peranteau WH, Endo M, Adibe OO, Flake AW. Evidence for an immune barrier after in utero hematopoietic-cell transplantation. Blood. 2007;109:1331–3.
Merianos DJ, Tiblad E, Santore MT, et al. Maternal alloantibodies induce a postnatal immune response that limits engraftment following in utero hematopoietic cell transplantation in mice. J Clin Invest. 2009;119:2590–600.
Lee PW, Cina RA, Randolph MA, et al. In utero bone marrow transplantation induces kidney allograft tolerance across a full major histocompatibility complex barrier in Swine. Transplantation. 2005;79:1084–90.
Peranteau WH, Heaton TE, Gu YC, et al. Haploidentical in utero hematopoietic cell transplantation improves phenotype and can induce tolerance for postnatal same-donor transplants in the canine leukocyte adhesion deficiency model. Biol Blood Marrow Transplant. 2009;15:293–305.
Blakemore K, Hattenburg C, Stetten G, et al. In utero hematopoietic stem cell transplantation with haploidentical donor adult bone marrow in a canine model. Am J Obstet Gynecol. 2004;190:960–73.
Omori F, Lutzko C, Abrams-Ogg A, et al. Adoptive transfer of genetically modified human hematopoietic stem cells into preimmune canine fetuses. Exp Hematol. 1999;27:242–9.
Shields LE, Gaur LK, Gough M, Potter J, Sieverkropp A, Andrews RG. In utero hematopoietic stem cell transplantation in nonhuman primates: the role of T cells. Stem Cells. 2003;21:304–14.
Tarantal AF, Goldstein O, Barley F, Cowan MJ. Transplantation of human peripheral blood stem cells into fetal rhesus monkeys (Macaca mulatta). Transplantation. 2000;69:1818–23.
Asano T, Ageyama N, Takeuchi K, et al. Engraftment and tumor formation after allogeneic in utero transplantation of primate embryonic stem cells. Transplantation. 2003;76:1061–7.
Almeida-Porada G, Porada C, Gupta N, Torabi A, Thain D, Zanjani ED. The human-sheep chimeras as a model for human stem cell mobilization and evaluation of hematopoietic grafts’ potential. Exp Hematol. 2007;35:1594–600.
Flake AW, Harrison MR, Adzick NS, Zanjani ED. Transplantation of fetal hematopoietic stem cells in utero: the creation of hematopoietic chimeras. Science. 1986;233:776–8.
Narayan AD, Chase JL, Lewis RL, et al. Human embryonic stem cell-derived hematopoietic cells are capable of engrafting primary as well as secondary fetal sheep recipients. Blood. 2006;107:2180–3.
Zanjani ED, Flake AW, Rice H, Hedrick M, Tavassoli M. Long-term repopulating ability of xenogeneic transplanted human fetal liver hematopoietic stem cells in sheep. J Clin Invest. 1994;93:1051–5.
Zanjani ED, Pallavicini MG, Ascensao JL, et al. Engraftment and long-term expression of human fetal hemopoietic stem cells in sheep following transplantation in utero. J Clin Invest. 1992;89:1178–88.
Liechty KW, MacKenzie TC, Shaaban AF, et al. Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med. 2000;6:1282–6.
Touraine JL, Raudrant D, Royo C, et al. In-utero transplantation of stem cells in bare lymphocyte syndrome. Lancet. 1989;1:1382.
Flake AW, Roncarolo MG, Puck JM, et al. Treatment of X-linked severe combined immunodeficiency by in utero transplantation of paternal bone marrow. N Engl J Med. 1996;335:1806–10.
Wengler GS, Lanfranchi A, Frusca T, et al. In-utero transplantation of parental CD34 haematopoietic progenitor cells in a patient with X-linked severe combined immunodeficiency (SCIDXI). Lancet. 1996;348:1484–7.
Touraine JL, Raudrant D, Laplace S. Transplantation of hematopoietic cells from the fetal liver to treat patients with congenital diseases postnatally or prenatally. Transplant Proc. 1997;29:712–3.
Gil J, Porta F, Bartolome J, et al. Immune reconstitution after in utero bone marrow transplantation in a fetus with severe combined immunodeficiency with natural killer cells. Transplant Proc. 1999;31:2581.
Pirovano S, Notarangelo LD, Malacarne F, et al. Reconstitution of T-cell compartment after in utero stem cell transplantation: analysis of T-cell repertoire and thymic output. Haematologica. 2004;89:450–61.
Mintz B, Anthony K, Litwin S. Monoclonal derivation of mouse myeloid and lymphoid lineages from totipotent hematopoietic stem cells experimentally engrafted in fetal hosts. Proc Natl Acad Sci USA. 1984;81:7835–9.
Czechowicz A, Kraft D, Weissman IL, Bhattacharya D. Efficient transplantation via antibody-based clearance of hematopoietic stem cell niches. Science. 2007;318:1296–9.
Stewart FM, Zhong S, Wuu J, Hsieh C, Nilsson SK, Quesenberry PJ. Lymphohematopoietic engraftment in minimally myeloablated hosts. Blood. 1998;91:3681–7.
Peranteau WH, Endo M, Adibe OO, Merchant A, Zoltick PW, Flake AW. CD26 inhibition enhances allogeneic donor-cell homing and engraftment after in utero hematopoietic-cell transplantation. Blood. 2006;108:4268–74.
Lindton B, Tolfvenstam T, Norbeck O, et al. Recombinant parvovirus B19 empty capsids inhibit fetal hematopoietic colony formation in vitro. Fetal Diagn Ther. 2001;16:26–31.
Flake AW, Zanjani ED. Cellular therapy. Obstet Gynecol Clin North Am. 1997;24:159–77.
Shaaban AF, Kim HB, Milner R, Flake AW. A kinetic model for the homing and migration of prenatally transplanted marrow. Blood. 1999;94:3251–7.
Taylor PA, McElmurry RT, Lees CJ, Harrison DE, Blazar BR. Allogenic fetal liver cells have a distinct competitive engraftment advantage over adult bone marrow cells when infused into fetal as compared with adult severe combined immunodeficient recipients. Blood. 2002;99:1870–2.
Peranteau WH, Hayashi S, Kim HB, Shaaban AF, Flake AW. In utero hematopoietic cell transplantation: what are the important questions? Fetal Diagn Ther. 2004;19:9–12.
Durkin ET, Jones KA, Elnaggar D, Shaaban AF. Donor major histocompatibility complex class I expression determines the outcome of prenatal transplantation. J Pediatr Surg. 2008;43:1142–7.
Donahue J, Gilpin E, Lee TH, Busch MP, Croft M, Carrier E. Microchimerism does not induce tolerance and sustains immunity after in utero transplantation. Transplantation. 2001;71:359–68.
Leung P, Gidari AS. Effect of aminoglutethimide on murine fetal hepatic erythroid colony formation. Experientia. 1985;41:498–500.
Roodman GD, Lee J, Gidari AS. Effects of dexamethasone on erythroid colony and burst formation from human fetal liver and adult marrow. Br J Haematol. 1983;53:621–8.
Golombeck K, Ball RH, Lee H, et al. Maternal morbidity after maternal-fetal surgery. Am J Obstet Gynecol. 2006;194:834–9.
Chou SH, Chawla A, Lee TH, et al. Increased engraftment and GVHD after in utero transplantation of MHC-mismatched bone marrow cells and CD80low, CD86(−) dendritic cells in a fetal mouse model. Transplantation. 2001;72:1768–76.
Misra MV, Gutweiler JR, Suh MY, et al. A murine model of graft-vs-host disease after in utero hematopoietic cell transplantation. J Pediatr Surg. 2009;44:1102–7; discussion 7.
Mackenzie TC, Shaaban AF, Radu A, Flake AW. Engraftment of bone marrow and fetal liver cells after in utero transplantation in MDX mice. J Pediatr Surg. 2002;37:1058–64.
Ye L, Chang JC, Lin C, Sun X, Yu J, Kan YW. Induced pluripotent stem cells offer new approach to therapy in thalassemia and sickle cell anemia and option in prenatal diagnosis in genetic diseases. Proc Natl Acad Sci USA. 2009;106:9826–30.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer-Verlag London
About this chapter
Cite this chapter
Nijagal, A., MacKenzie, T.C. (2013). In Utero Hematopoietic Stem Cell Transplantation for Congenital Disorders. In: Bhattacharya, N., Stubblefield, P. (eds) Human Fetal Tissue Transplantation. Springer, London. https://doi.org/10.1007/978-1-4471-4171-6_12
Download citation
DOI: https://doi.org/10.1007/978-1-4471-4171-6_12
Published:
Publisher Name: Springer, London
Print ISBN: 978-1-4471-4170-9
Online ISBN: 978-1-4471-4171-6
eBook Packages: MedicineMedicine (R0)