Human umbilical cord blood: A clinically useful source of transplantable hematopoietic stem/progenitor cells

Abstract

This is a review and discussion of studies leading to the first use of human umbilical cord blood, material usually discarded, for the provision of stem/progenitor cells for clinical hematopoietic reconstitution. This prospect arose as a result of extensive studies of the harvesting and cryopreservation of cord blood and of its numerical content of progenitor cells demonstrable in vitro. A male patient with Fanconi anemia (FA) was conditioned with a modified regimen of cyclophosphamide and irradiation that accommodates the abnormally high sensitivity to these agents that is characteristic of FA. Cryopreserved cord blood had been retrieved at birth from a female sibling known from prenatal testing to be unaffected by FA and to be human leukocyte antigen (HLA)-compatible with the prospective sibling recipient. After conditioning and therapeutic infusion of thawed cord blood, successful hematopoietic reconstitution was indicated by the general health of the patient, who had previously required supportive transfusions, by satisfactory hematological criteria and by counts of hematopoietic progenitor cells of various types in the bone marrow. Complete engraftment of the myeloid system with donor cells was evident from cytogenetics, ABO typing, study of DNA polymorphisms, and normal cellular resistance to cytotoxic agents that reveal the fragility of FA cells; the blood contained a residuum of host lymphocytes exhibiting chromosomal damage, but the trend has been towards eliminating these damaged cells. This implies that cord blood from a single individual should provide sufficient reconstituting cells for effective hematopoietic repopulation of an autologous or an HLA-compatible allogeneic recipient.

Differential growth factor requirement of primitive cord blood hematopoietic stem cell for self-renewal and amplification vs proliferation and differentiation

“…of Biomedical Sciences and Human Oncology, Clinica Medica I, Via Genova 3, 10126 Torino, Italy; Fax: 39 11 6637 238 Received 17 November 1997; accepted 23 January 1998 are characterized by an ability to generate very large numbers (Ͼ10 13 ) of all known mature blood cell types. [1][2][3][4] In both mouse and human systems, a subset of extremely primitive hematopoietic cells has been identified because of its ability to generate clonogenic cells (colony-forming cells (CFC)) for at least 5 weeks on suitable stroma feeder layers of murine or human origin. 5 These long-term culture-initiating cells (LTCICs) share a number of features with long-term in vivo repopulating cells.…”

High-efficiency recovery of functional hematopoietic progenitor and stem cells from human cord blood cryopreserved for 15 years

“…Since our initial preclinical (14)(15)(16) and clinical (1,(17)(18)(19) studies, there have been Ͼ2,000 CB transplants performed to treat a variety of malignant and nonmalignant disorders in children and adults (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(17)(18)(19). CB HSC͞HPC are frozen before use for transplantation (14,(20)(21)(22), but the longest that a CB collection has been stored frozen before use for clinical transplantation is in the 3-to 5-yr range.…”

Cord Blood Banking: The Prospects and Challenges of Implementation in Nigeria

“…It currently constitutes an increasingly used alternative to bone marrow transplantation. A few other conditions do benefit from stem cell therapy, but the therapeutic role in a large number of conditions is at present still only speculative [4]. Cord blood hematopoietic stem cells (HSCs) are relatively easy to isolate, giving them an advantage over other adult stem cell types.…”