Fetal Stem Cells: Betwixt and Between

ABSTRACT

Fetal stem cells can be isolated not only from fetal blood and hemopoietic organs in early pregnancy, but from a variety of somatic organs as well as amniotic fluid and placenta throughout gestation. Fetal blood is a rich source of hemopoietic stem cells, which proliferate more rapidly than those in cord blood or adult bone marrow. First-trimester fetal blood, liver, and bone marrow also contain a population of mesenchymal stem cells, which appear to be more primitive with greater multipotentiality than their adult counterparts. Fetal stem cells may thus represent an intermediate cell type in the current debate focusing on dichotomized adult versus embryonic stem cells, and thus prove advantageous as a source for downstream cell therapy applications. They have also been implicated in fetomaternal trafficking in pregnancy, and in long-term microchimerism in postreproductive women.

KEYWORDS

Fetal tissue - fetal and cord blood - mesenchymal stem cell - hemopoietic stem cell - fetal therapy - fetomaternal microchimerism

REFERENCES

• 1 Prindull G, Zipori D. Environmental guidance of normal and tumor cell plasticity: epithelial mesenchymal transitions as a paradigm.  Blood. 2004;  103(8) 2892-2899
• 2 Sanchez-Ramos J. Stem cells from cord blood.  Semin Reprod Med. 2006;  24 358-369
• 3 Campagnoli C, Fisk N, Overton T, Bennett P, Watts T, Roberts I. Circulating hematopoietic progenitor cells in first trimester fetal blood.  Blood. 2000;  95(6) 1967-1972
• 4 Campagnoli C, Roberts I A, Kumar S, Bennett P R, Bellantuono I, Fisk N M. Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow.  Blood. 2001;  98(8) 2396-2402
• 5 Orlandi F, Damiani G, Jakil C, Lauricella S, Bertolino O, Maggio A. The risks of early cordocentesis (12-21 weeks): analysis of 500 procedures.  Prenat Diagn. 1990;  10(7) 425-428
• 6 Surbek D V, Tercanli S, Holzgreve W. Transabdominal first trimester embryofetoscopy as a potential approach to early in utero stem cell transplantation and gene therapy.  Ultrasound Obstet Gynecol. 2000;  15(4) 302-307
• 7 Surbek D V, Young A, Danzer E, Schoeberlein A, Dudler L, Holzgreve W. Ultrasound-guided stem cell sampling from the early ovine fetus for prenatal ex vivo gene therapy.  Am J Obstet Gynecol. 2002;  187(4) 960-963
• 8 Huss R. Isolation of primary and immortalized CD34-hematopoietic and mesenchymal stem cells from various sources.  Stem Cells. 2000;  18(1) 1-9
• 9 Taylor P A, McElmurry R T, Lees C J, Harrison D E, Blazar B R. 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(5) 1870-1872
• 10 Clapp D W, Freie B, Lee W H, Zhang Y Y. Molecular evidence that in situ-transduced fetal liver hematopoietic stem/progenitor cells give rise to medullary hematopoiesis in adult rats.  Blood. 1995;  86(6) 2113-2122
• 11 O'Donoghue K, Fisk N M. Fetal stem cells.  Best Pract Res Clin Obstet Gynaecol. 2004;  18(6) 853-875
• 12 Tocci A, Forte L. Mesenchymal stem cell: use and perspectives.  Hematol J. 2003;  4(2) 92-96
• 13 Lim F T, Kanhai H H, Falkenburg J H. Characterization of the human CD34 + hematopoietic progenitor cell compartment during the second trimester of pregnancy.  Haematologica. 2005;  90(2) 173-179
• 14 De la Fuente J, O'Donoghue K, Kumar S, Chan J, Fisk N M, Roberts I A. Ontogeny-related changes in integrin expression and cytokine production by fetal mesenchymal stem cells (MSC).  Blood. 2002;  100(11) 526a
• 15 Lee J, Elkahloun A G, Messina S A et al.. Cellular and genetic characterization of human adult bone marrow-derived neural stem-like cells: a potential antiglioma cellular vector.  Cancer Res. 2003;  63(24) 8877-8889
• 16 Mareschi K, Biasin E, Piacibello W, Aglietta M, Madon E, Fagioli F. Isolation of human mesenchymal stem cells: bone marrow versus umbilical cord blood.  Haematologica. 2001;  86(10) 1099-1100
• 17 Erices A, Conget P, Minguell J J. Mesenchymal progenitor cells in human umbilical cord blood.  Br J Haematol. 2000;  109(1) 235-242
• 18 Yu M, Xiao Z, Shen L, Li L. Mid-trimester fetal blood-derived adherent cells share characteristics similar to mesenchymal stem cells but full-term umbilical cord blood does not.  Br J Haematol. 2004;  124(5) 666-675
• 19 Rollini P, Kaiser S, Faes-van't Hull E, Kapp U, Leyvraz S. Long-term expansion of transplantable human fetal liver hematopoietic stem cells.  Blood. 2004;  103(3) 1166-1170
• 20 Nicolini U, Poblete A. Single intrauterine death in monochorionic twin pregnancies.  Ultrasound Obstet Gynecol. 1999;  14 297-301
• 21 Zanjani E D, Ascensao J L, Tavassoli M. Liver-derived fetal hematopoietic stem cells selectively and preferentially home to the fetal bone marrow.  Blood. 1993;  81(2) 399-404
• 22 Holyoake T L, Nicolini F E, Eaves C J. Functional differences between transplantable human hematopoietic stem cells from fetal liver, cord blood, and adult marrow.  Exp Hematol. 1999;  27(9) 1418-1427
• 23 Nava S, Westgren M, Jaksch M et al.. Characterization of cells in the developing human liver.  Differentiation. 2005;  73(5) 249-260
• 24 Gotherstrom C, West A, Liden J, Uzunel M, Lahesmaa R, Le Blanc K. Difference in gene expression between human fetal liver and adult bone marrow mesenchymal stem cells.  Haematologica. 2005;  90(8) 1017-1026
• 25 in ‘t Anker P, Noort W A, Scherjon S A et al.. Mesenchymal stem cells in human second-trimester bone marrow, liver, lung, and spleen exhibit a similar immunophenotype but a heterogeneous multilineage differentiation potential.  Haematologica. 2003;  88(8) 845-852
• 26 Goossens E, Tournaye H. Testicular stem cells.  Semin Reprod Med. 2006;  24 370-378
• 27 Le Blanc K, Gotherstrom C, Ringden O et al.. Fetal mesenchymal stem-cell engraftment in bone after in utero transplantation in a patient with severe osteogenesis imperfecta.  Transplantation. 2005;  79(11) 1607-1614
• 28 Zanjani E D, Pallavicini M G, Ascensao J L et al.. Engraftment and long-term expression of human fetal hemopoietic stem cells in sheep following transplantation in utero.  J Clin Invest. 1992;  89(4) 1178-1188
• 29 in ‘t Anker P S, Noort W A, Kruisselbrink A B et al.. Nonexpanded primary lung and bone marrow-derived mesenchymal cells promote the engraftment of umbilical cord blood-derived CD34( + ) cells in NOD/SCID mice.  Exp Hematol. 2003;  31(10) 881-889
• 30 Hu Y, Liao L, Wang Q et al.. Isolation and identification of mesenchymal stem cells from human fetal pancreas.  J Lab Clin Med. 2003;  141(5) 342-349
• 31 Huang H, Tang X. Phenotypic determination and characterization of nestin-positive precursors derived from human fetal pancreas.  Lab Invest. 2003;  83(4) 539-547
• 32 Yao Z X, Qin M L, Liu J J, Chen X S, Zhou D S. In vitro cultivation of human fetal pancreatic ductal stem cells and their differentiation into insulin-producing cells.  World J Gastroenterol. 2004;  10(10) 1452-1456
• 33 Al-Awqati Q, Oliver J A. Stem cells in the kidney.  Kidney Int. 2002;  61(2) 387-395
• 34 Almeida-Porada G, El Shabrawy D, Porada C, Zanjani E D. Differentiative potential of human metanephric mesenchymal cells.  Exp Hematol. 2002;  30(12) 1454-1462
• 35 Almeida-Porada G, Porada C, Esmail D. Differentiation potential of human metanephric stem cells: from mesenchyme to blood.  Blood. 2000;  96 494a
• 36 Almeida-Porada G, Crapnell K, Porada C et al.. In vivo haematopoietic potential of human neural stem cells.  Br J Haematol. 2005;  130 276-283
• 37 Fauza D. Amniotic fluid and placental stem cells.  Best Pract Res Clin Obstet Gynaecol. 2004;  18(6) 877-891
• 38 Kaviani A, Guleserian K, Perry T E, Jennings R W, Ziegler M M, Fauza D O. Fetal tissue engineering from amniotic fluid.  J Am Coll Surg. 2003;  196(4) 592-597
• 39 Tsai M S, Lee J L, Chang Y J, Hwang S M. Isolation of human multipotent mesenchymal stem cells from second-trimester amniotic fluid using a novel two-stage culture protocol.  Hum Reprod. 2004;  19(6) 1450-1456
• 40 in ‘t Anker P S, Scherjon S A, Kleijburg-van der Keur C et al.. Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation.  Blood. 2003;  102(4) 1548-1549
• 41 Zhao P, Ise H, Hongo M, Ota M, Konishi I, Nikaido T. Human amniotic mesenchymal cells have some characteristics of cardiomyocytes.  Transplantation. 2005;  79(5) 528-535
• 42 Haigh T, Chen C, Jones C J, Aplin J D. Studies of mesenchymal cells from 1st trimester human placenta: expression of cytokeratin outside the trophoblast lineage.  Placenta. 1999;  20(8) 615-625
• 43 Zhang Y, Li C, Jiang X, Li H, Tang P, Mao N. Comparison of mesenchymal stem cells from human placenta and bone marrow.  Chin Med J (Engl). 2004;  117(6) 882-887
• 44 Li C D, Zhang W Y, Li H L et al.. Isolation and identification of a multilineage potential mesenchymal cell from human placenta. Placenta 2005 [Epub ahead of print]
• 45 Young H E, Steele T A, Bray R A et al.. Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors.  Anat Rec. 2001;  264(1) 51-62
• 46 Valerio D, Altieri V, Antonucci F R, Aiello R. Characterization of fetal haematopoietic progenitors circulating in maternal blood of seven aneuploid pregnancies.  Prenat Diagn. 1997;  17(12) 1159-1169
• 47 Campagnoli C, Roberts I A, Kumar S et al.. Expandability of haemopoietic progenitors in first trimester fetal and maternal blood: implications for non-invasive prenatal diagnosis.  Prenat Diagn. 2002;  22(6) 463-469
• 48 O'Donoghue K, Choolani M, Chan J et al.. Identification of fetal mesenchymal stem cells in maternal blood: implications for non-invasive prenatal diagnosis.  Mol Hum Reprod. 2003;  9(8) 497-502
• 49 Bianchi D W, Zickwolf G K, Weil G J, Sylvester S, DeMaria M A. Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum.  Proc Natl Acad Sci USA. 1996;  93(2) 705-708
• 50 O'Donoghue K, Chan J, de la Fuente J et al.. Microchimerism in female bone marrow and bone decades after fetal mesenchymal stem-cell trafficking in pregnancy.  Lancet. 2004;  364(9429) 179-182
• 51 Khosrotehrani K, Bianchi D W. Fetal cell microchimerism: helpful or harmful to the parous woman?.  Curr Opin Obstet Gynecol. 2003;  15(2) 195-199
• 52 Srivatsa B, Srivatsa S, Johnson K L, Samura O, Lee S L, Bianchi D W. Microchimerism of presumed fetal origin in thyroid specimens from women: a case-control study.  Lancet. 2001;  358(9298) 2034-2038
• 53 Khosrotehrani K, Johnson K L, Cha D H, Salomon R N, Bianchi D W. Transfer of fetal cells with multilineage potential to maternal tissue.  JAMA. 2004;  292(1) 75-80
• 54 Khosrotehrani K, Johnson K L, Lau J, Dupuy A, Cha D H, Bianchi D W. The influence of fetal loss on the presence of fetal cell microchimerism: a systematic review.  Arthritis Rheum. 2003;  48(11) 3237-3241
• 55 Khosrotehrani K, Bianchi D. Multi-lineage potential of fetal cells in maternal tissue: a legacy in reverse.  J Cell Sci. 2005;  118 1559-1563
• 56 MacKenzie T S, Campagnoli C, Almeida-Porada G, Fisk N M, Flake A W. Circulating human fetal stromal cells engraft and differentiate in multiple tissues following transplantation into pre-immune fetal lambs.  Blood. 2001;  98 328a
• 57 de la Fuente J, Fisk N, O'Donoghue K, Chan J, Kumar S, Roberts I. α2β1 and α4β1 integrins mediate the homing of mesenchymal stem/progenitor cells during fetal life.  Haematol J. 2003;  4(suppl 2) 13
• 58 Gotherstrom C, Ringden O, Tammik C, Zetterberg E, Westgren M, Le Blanc K. Immunologic properties of human fetal mesenchymal stem cells.  Am J Obstet Gynecol. 2004;  190(1) 239-245
• 59 Chan J, O'Donoghue K, de la Fuente J et al.. Human fetal mesenchymal stem cells as vehicles for gene delivery.  Stem Cells. 2005;  23(1) 93-102
• 60 Schoeberlein A, Holzgreve W, Dudler L, Hahn S, Surbek D V. Tissue-specific engraftment after in utero transplantation of allogeneic mesenchymal stem cells into sheep fetuses.  Am J Obstet Gynecol. 2005;  192(4) 1044-1052
• 61 Mackenzie T C, Shaaban A F, Radu A, Flake A W. Engraftment of bone marrow and fetal liver cells after in utero transplantation in MDX mice.  J Pediatr Surg. 2002;  37(7) 1058-1064
• 62 Fukada S, Miyagoe-Suzuki Y, Tsukihara H et al.. Muscle regeneration by reconstitution with bone marrow or fetal liver cells from green fluorescent protein-gene transgenic mice.  J Cell Sci. 2002;  115(pt 6) 1285-1293
• 63 in ‘t Anker P S, Scherjon S A, Kleijburg-van der Keur C et al.. Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta.  Stem Cells. 2004;  22(7) 1338-1345