Abstract
Hematopoietic stem cell transplantation has been increasingly used to replace a defective hematopoietic system and to treat various genetic defects as well as malignant diseases. However, the limitations of conventional bone marrow transplantation have stimulated an intense interest in exploring the use of alternative sources of hematopoietic stem cells, including peripheral blood mononuclear cells (PBMC) and cord blood (CB). A major investigative effort of our laboratory has been focused on evaluating fetal bone marrow (FBM) for transplantation. The current study compares and characterizes the functional and phenotypic characteristics of FBM, CB, adult bone marrow (ABM), and PBMC by clonogenicity assays, immunogenicity, and the quantification of progenitor cells. There was a striking difference in the proportion of CD34+ cells in FBM, ABM, PBMC, and CB (24.6%, 2.1%, 0.5%, and 2.0%, respectively). The clonogenic potential, as measured by colony forming unit in culture (CFU-C) assay, was significantly higher in FBM when compared with ABM, PBMC, and CB (202.5, 73.5, 40.8, and 65.5 colonies/105 cells, respectively). There was a significant decrease in proliferative responsiveness in mixed lymphocyte reaction (MLR) assay of FBM and CB compared with ABM and PBMC. These observations indicate that each source of hematopoietic stem cells has different intrinsic properties closely correlated with ontogenetic age that is a vital determinant for phenotypic characteristics, lineage commitments, immunogenicity, and proliferative potentials.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- BFU-E:
-
burst-forming unit - erythrocyte
- CFU-C:
-
colony forming unit in culture
- CFU-GM:
-
colony-forming unit - granulocyte macrophage
- FBM:
-
fetal bone marrow
- ABM:
-
adult bone marrow
- CB:
-
cord blood
- GVHD:
-
graft versus host disease
- PBSC:
-
peripheral blood stem cell
References
Leonard ZI 1995 Developmental biology of hematopoiesis. Blood 86: 2876–2891
Metcalf D, More MAS 1971 Embryonic aspects of hematopoiesis. In: Neuberger A, Tatum EL (eds) Frontiers of Biology-Hematopoietic Cells. North Holland Publishing Co, Amsterdam, pp 172–271
Michejda M 1988 Utilization of fetal tissue in transplantation. Fetal Ther 21: 129–134
Michejda M 1990 CNS repair. In: Harrison M, Golbus M, Filly R (eds) Unborn Patient, 2nd Ed. W. Saunders, Philadelphia, pp 565–580
Breeze RE, Wells TH Jr, Freed CR 1995 Implantation of fetal tissue for the management of Parkinson's disease: a technical note. Neurosurgery 36: 1044–1048
Leor J, Patterson M, Quinones MJ, Kedes LH, Kloner RA 1996 Transplantation of fetal myocardial tissue into the infarcted myocardium of rat: a potential method for repair of infarcted myocardium?. Circulation 94( suppl 9): II332–336
Beattie GM, Otonkoski T, Lopez AD, Hayek A 1997 Functional beta-cell mass after transplantation of human fetal pancreatic cells: differentiation or proliferation?. Diabetes 46: 244–248
Anderson DK, Howland DR, Reier PJ 1995 Fetal neural grafts and repair of the injured spinal cord. Brain Pathol 5: 451–457
Talmadge JE, Reed E, Ino K, Kessinger A, Kuszynski C, Heimann D, Varney M, Jackson J, Vose JM, Bierman PJ 1997 Rapid immunologic reconstitution following transplantation with mobilized peripheral blood stem cells as compared to bone marrow. Bone Marrow Transplant 19: 161–172
Koehne G, Zeller W, Stockschlaeder M, Zander AR 1997 Phenotype of lymphocyte subsets after autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 19: 149–156
Gluckman E, Rocha V, Boyer-Chammard A, Locatelli F, Arcese W, Pasquini R, Ortega J, Souillet G, Ferreira E, Laporte JP, Fernandez M, Chastang C 1997 Outcome of cord-blood transplantation from related and unrelated donors. N Engl J Med 337: 373–381
Gluckman E, Broxmeyer HE, Auerbach A, Douglas GW, Devergie A, Esperou H, Thierry D, Socie G, Lehn P, Cooper S, English D, Kurzberg J, Bard J, Boye EA 1989 Hematopoietic reconstitution in a patient with Fanconi's anemia by means of umbilical cord blood from HLA-identical sibling. N Engl J Med 321: 1174–1178
Broxmeyer HE, Douglas GW, Hangoc G, Cooper S, Bard J, English D, Arny M, Thomas L, Boys EA 1989 Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells. Proc Natl Acad Sci USA 86: 3828–3832
Thoma SJ, Lamping CP, Ziegler BL 1994 Phenotype analysis of hematopoietic CD34+ cell populations derived from human umbilical cord blood using flow cytometry and cDNA-polymerase chain reaction. Blood 83: 2103–2014
Briz M, Regidor C, Monteagudo D, Somolinos N, Garaulet C, Fores R, Posada M, Fernandez MN 1998 Detection of maternal DNA in umbilical cord blood by polymerase chain reaction amplification of minisatellite sequences. Bone Marrow Transplant 21: 1097–1099
Cairo MS, Wagner JE 1997 Placental and/or umbilical cord blood: an alternative source of hematopoietic stem cells for transplantation. Blood 90: 4665–4678
Thomas ED, Storb R 1970 Technique for human marrow grafting. Blood 36: 507–515
Batinic D, Marusic M, Pavletic Z, Bogdanic V, Uzarevic B, Nemet D, Labar B 1990 Relationship between differing volumes of bone marrow aspirates and their cellular composition. Bone Marrow Transplant 6: 103–107
Holdrinet RSG, van Egmond J, Wessels JMC, Haanen C 1980 A method for quantification of peripheral blood admixture in bone marrow aspirates. Exp Hematol 8: 103–107
Scheffe H 1959 The Analysis of Variance. John Wiley & Sons, Inc, New York pp 73–77
Conrad PD, Emerson SG 1998 Ex vivo expansion of hematopoietic cells from umbilical cord blood for clinical transplantation. J Leukoc Biol 64: 147–155
Gian VG, Moreb JS, Abdel-Mageed A, Weeks FM, Scornick JC, Winggard JR 1998 Successful salvage using mismatched umbilical cord blood transplant in an adult with recurrent acute myelogenous leukemia failing autologous peripheral blood progenitor cell transplant: a case history and review. Bone Marrow Transplant 21: 1197–1200
Gale RP 1992 Fetal liver transplants. Bone Marrow Transplant 21: 1197–1200
Landsdorp PM, Dragowska W, Mayani H 1993 Ontogeny-related changes in proliferative potential of human hematopoietic cells. J Exp Med 178: 787–791
Kurtzberg J, Laughlin M, Graham ML, Smith C, Oslon JF, Halperin EC, Ciocci G, Carrier C, Stevens CE, Rubinstein P 1996 Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients. N Engl J Med 335: 157–166
Kessinger A, Armitage JO, Landmark JD, Smith DM, Weisenburger DD 1988 Autologous peripheral hematopoietic stem cell transplantation restores hematopoietic function following marrow ablative therapy. Blood 71: 723–727
Cleveland WW, Fogel BJ, Brown WT, Kay HEM 1968 Foetal thymic transplant in a case of Digeorge's syndrome. Lancet 2: 1211–1214
Steele RW, Limas C, Thurman GB, Schuellin M, Bauer H, Bellanti JA 1972 Familial thymic aplasia: attempt reconstitution with fetal thymus in a Millipore diffusion chamber. N Engl J Med 287: 787–791
Harris DT, Schumacher MJ, Locasio J, Besencon FJ, Olson GB, De Luca D, Shenker L, Bard J, Boyse EA 1992 Phenotypic and functional immaturity of human umbilical cord blood T lymphocytes. Proc Natl Acad Sci USA 89: 10006–10010
Ema H, Suda T, Miura Y, Nakauchi H 1990 Colony formation of clone-sorted human hematopoietic progenitors. Blood 75: 1941–1946
Saeland S, Duvert V, Caux C, Pandrau D, Favre C, Vallé A, Durand I, Charbord P, deVries J, Banchereau J 1992 Distribution of surface-membrane molecules on bone marrow and cord blood CD34+ hematopoietic cells. Exp Hematol 20: 24–33
Sasazuki T, Juji T, Morihima Y, Kinukawa N, Kashiwabara H, Inoko H, Yoshida T, Kimura A, Akaza T, Kamikawaji N, Kodera Y, Takaku F 1998 Effect of matching of cells from an unrelated donor. N Engl J Med 339: 1177–1185
Kessinger A, Armitage JO 1991 The evolving role of autologous peripheral stem cell transplantation following high-dose chemotherapy for malignancies. Blood 77: 211–213
Bensinger WI, Weaver CH, Appelbaum FR, Rowley S, Demirer T, Sanders J, Storb R, Buckner CD 1991 Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant human granulocyte colony-stimulating factor. Blood 85: 1655–1658
Simmons PJ, Torok-Storb B 1991 CD34 expression by stromal precursors in normal human adult bone marrow. Blood 78: 2848–2853
Srour EF, Brand JE, Briddell RA, Leemhuis T, van Besien K, Hoffman R 1991 Human CD34+ HLA-DR- bone marrow cells contain progenitor cells capable of self-renewal, multi lineage differentiation, and long term in vitro hematopoiesis. Blood Cells 17: 287–295
Denis E, Bender J, Lee W, Schilling M, Smith S, Unerzagt K, Law P, Burgess J 1994 Harvesting, characterization, and culture of CD34+ cells from human bone marrow, peripheral blood, and cord blood. Blood Cells 20: 411–423
Hao QL, Shah AJ, Thiemann FT, Smogorzewska EM, Crooks GM 1995 A functional comparison of CD34+CD38- cells in cord blood and bone marrow. Blood 86: 3745–3753
Traycoff CM, Abboud MR, Laver J, Brandt JE, Hoffman R, Law P, Ishizawa L, Srour EF 1994 Evaluation of the in vitro behavior of phenotypically defined populations of umbilical cord blood hematopoietic progenitor cells. Exp Hematol 22: 215–222
Terstappen LW, Huang S 1994 Analysis of bone marrow stem cell. Blood Cells 20: 45–63
Huang S, Terstappen LW 1994 Lymphoid and myeloid differentiation of single human CD34+, HLA-DR+, CD38- hematopoietic stem cells. Blood 83: 1515–1526
Clement LT, Vink PE, Bradley GE 1990 Novel immunoregulatory functions of phenotypically distinct subpopulations of CD4+ cells in the human neonate. J Immunol 145: 102–108
Lansdorp PM 1995 Developmental changes in the function of hematopoietic stem cells. Exp Hematol 23: 187–191
Michejda M, Peters SM, Bellanti JA 1992 Xenotransplantation, bone marrow transplantation and stem cell reconstitution. Transplantation 54: 759–762
Michejda M, Bacher J, Kuwabara T, Hodgen GD 1981 In utero allogeneic bone marrow transplantation in primates: roentgenographic and histologic observation. Transplantation 32: 96–100
Michejda M, Quo V 1996 Quo vadis? Fetal tissue transplantation. J Hematother 5: 185–188
Michejda M, Verma UN, Mazumder M, Wu AG 1996 Comparative study of hematopoietic precursors from fetal and adult bone marrow. Fetal Diagn ther 11: 52–61
Low WC, Eastlund T, Verfaille C 1994 Human fetal tissue from spontaneous abortion as potential sources of donor tissue for cell transplantation therapies. Transplant Proc 26: 3400–3406
Tocci A, Menichella G, Peretta G, Mancuso S 1994 Fetal tissue collection from spontaneous abortions: a report from a single center. Fetal Diagn Ther 6: 264–268
Touraine JL, Royo C, Rocarolo MG 1989 Unmatched stem cells transplantation as a possible alternative to bone marrow transplantation. Transplant Proc 21: 3112–3113
Touraine JL 1993 Transplantation of fetal liver stem cells into patients and into human fetuses with induction of immunologic tolerance. Transplant Proc 25: 1012–1013
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wu, A., Michejda, M., Mazumder, A. et al. Analysis and Characterization of Hematopoietic Progenitor Cells from Fetal Bone Marrow, Adult Bone Marrow, Peripheral Blood, and Cord Blood. Pediatr Res 46, 163–169 (1999). https://doi.org/10.1203/00006450-199908000-00006
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-199908000-00006
This article is cited by
-
Unbiased phenotypic identification of functionally distinct hematopoietic progenitors
Journal of Biological Research-Thessaloniki (2019)
-
Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain
BMC Neuroscience (2008)


