Growth characteristics and expansion of human umbilical cord blood and estimation of its potential for transplantation in adults

Hal Broxmeyer, Giao Hangoc, Scott Cooper, Raul C. Ribeiro, Vicki Graves, Mervin Yoder, John Wagner, Saroj Vadhan-Raj, Lisa Benninger, Pablo Rubinstein, E. Randolph Broun

Research output: Contribution to journalArticle

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Abstract

We estimated whether single collections of cord blood contained sufficient cells for hematopoietic engraftment of adults by evaluating numbers of cord blood and adult bone marrow myeloid progenitor cells (MPCs) as detected in vitro with steel factor (SLF) and hematopoietic colonystimulating factors (CSFs). SLF plus granulocyte-macrophage (GM)-CSF detected 8- to 11-fold more cord blood GM progenitors [colony-forming units (CFU)-GM] than cells stimulated with GM-CSF or 5637 conditioned medium (CM), growth factors previously used to estimate cord blood CFU-GM numbers. SLF plus erythropoietin (Epo) plus interleukin 3 (IL-3) enhanced detection of cord blood multipotential (CFU-GEMM) progenitors 15-fold compared to stimulation with Epo plus IL-3. Under the same conditions, bone marrow CFU-GM and CFU-GEMM were only enhanced in detection 2- to 4- and 6- to 8-fold. Increased detection of cord blood CFU-GEMM correlated directly with decreased detection of cord blood erythroid burst-forming units (BFU-E). In contrast, adult bone marrow CFU-GEMM and BFU-E numbers were both enhanced by SLF plus Epo plus IL-3. This suggests that most cord blood BFU-E may actually be CFU-GEMM. Cord blood collections (n = 17) contained numbers of MPCs (especially CFU-GM) similar to the number found in nine autologous bone marrow collections. To assess additional sources of MPCs, the peripheral blood of 1-day-old infants was assessed. However, average concentrations of MPCs circulating in these infants were only 30-46% that in their cord blood. Expansion of cord blood MPCs was also evaluated. Incubation of cord blood cells for 7 days with SLF resulted in 7.9-, 2.2-, and 2.7-fold increases in numbers of CFU-GM, BFU-E, and CFU-GEMM compared to starting numbers; addition of a CSF with SLF resulted in even greater expansion of MPCs. The results suggest that cord blood contains a larger number of early profile MPCs than previously recognized and that there are probably sufficient numbers of cells in a single cord blood collection to engraft an adult. Although the expansion data must be considered with caution, as human marrow repopulating cells cannot be assessed directly, in vitro expansion of cord blood stem and progenitor cells may be feasible for clinical transplantation.

Original languageEnglish
Pages (from-to)4109-4113
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number9
StatePublished - 1992

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Fetal Blood
Transplantation
Myeloid Progenitor Cells
Growth
Granulocyte-Macrophage Progenitor Cells
Stem Cell Factor
Stem Cells
Erythroid Precursor Cells
Interleukin-3
Erythropoietin
Bone Marrow
Granulocytes
Blood Cells
Macrophages
Conditioned Culture Medium
Bone Marrow Cells
Intercellular Signaling Peptides and Proteins
Cell Count

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Growth characteristics and expansion of human umbilical cord blood and estimation of its potential for transplantation in adults. / Broxmeyer, Hal; Hangoc, Giao; Cooper, Scott; Ribeiro, Raul C.; Graves, Vicki; Yoder, Mervin; Wagner, John; Vadhan-Raj, Saroj; Benninger, Lisa; Rubinstein, Pablo; Broun, E. Randolph.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 9, 1992, p. 4109-4113.

Research output: Contribution to journalArticle

Broxmeyer, H, Hangoc, G, Cooper, S, Ribeiro, RC, Graves, V, Yoder, M, Wagner, J, Vadhan-Raj, S, Benninger, L, Rubinstein, P & Broun, ER 1992, 'Growth characteristics and expansion of human umbilical cord blood and estimation of its potential for transplantation in adults', Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 9, pp. 4109-4113.
Broxmeyer, Hal ; Hangoc, Giao ; Cooper, Scott ; Ribeiro, Raul C. ; Graves, Vicki ; Yoder, Mervin ; Wagner, John ; Vadhan-Raj, Saroj ; Benninger, Lisa ; Rubinstein, Pablo ; Broun, E. Randolph. / Growth characteristics and expansion of human umbilical cord blood and estimation of its potential for transplantation in adults. In: Proceedings of the National Academy of Sciences of the United States of America. 1992 ; Vol. 89, No. 9. pp. 4109-4113.
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AU - Graves, Vicki

AU - Yoder, Mervin

AU - Wagner, John

AU - Vadhan-Raj, Saroj

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AU - Rubinstein, Pablo

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N2 - We estimated whether single collections of cord blood contained sufficient cells for hematopoietic engraftment of adults by evaluating numbers of cord blood and adult bone marrow myeloid progenitor cells (MPCs) as detected in vitro with steel factor (SLF) and hematopoietic colonystimulating factors (CSFs). SLF plus granulocyte-macrophage (GM)-CSF detected 8- to 11-fold more cord blood GM progenitors [colony-forming units (CFU)-GM] than cells stimulated with GM-CSF or 5637 conditioned medium (CM), growth factors previously used to estimate cord blood CFU-GM numbers. SLF plus erythropoietin (Epo) plus interleukin 3 (IL-3) enhanced detection of cord blood multipotential (CFU-GEMM) progenitors 15-fold compared to stimulation with Epo plus IL-3. Under the same conditions, bone marrow CFU-GM and CFU-GEMM were only enhanced in detection 2- to 4- and 6- to 8-fold. Increased detection of cord blood CFU-GEMM correlated directly with decreased detection of cord blood erythroid burst-forming units (BFU-E). In contrast, adult bone marrow CFU-GEMM and BFU-E numbers were both enhanced by SLF plus Epo plus IL-3. This suggests that most cord blood BFU-E may actually be CFU-GEMM. Cord blood collections (n = 17) contained numbers of MPCs (especially CFU-GM) similar to the number found in nine autologous bone marrow collections. To assess additional sources of MPCs, the peripheral blood of 1-day-old infants was assessed. However, average concentrations of MPCs circulating in these infants were only 30-46% that in their cord blood. Expansion of cord blood MPCs was also evaluated. Incubation of cord blood cells for 7 days with SLF resulted in 7.9-, 2.2-, and 2.7-fold increases in numbers of CFU-GM, BFU-E, and CFU-GEMM compared to starting numbers; addition of a CSF with SLF resulted in even greater expansion of MPCs. The results suggest that cord blood contains a larger number of early profile MPCs than previously recognized and that there are probably sufficient numbers of cells in a single cord blood collection to engraft an adult. Although the expansion data must be considered with caution, as human marrow repopulating cells cannot be assessed directly, in vitro expansion of cord blood stem and progenitor cells may be feasible for clinical transplantation.

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