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Hematopoietic potential of cryopreserved and ex vivo manipulated umbilical
cord blood progenitor cells evaluated in vitro and in vivo
DL DiGiusto, R Lee, J Moon, K Moss, T O'Toole, A Voytovich, D Webster and JJ Mule
Progenesys Gene Therapy Group, Systemix Inc, Palo Alto, CA, USA.
The hematopoietic potential of cryopreserved and ex vivo manipulated
umbilical cord blood (UCB) samples was evaluated in vitro and in vivo.
Phenotypic analysis shows that approximately 1% of cord blood mononuclear
cells express high levels of CD34 antigen on their surface (CD34hi), but
none of a panel of lineage antigens (Lin-), suggesting that they are
hematopoietic progenitor cells that have not yet committed to a specific
lineage. Approximately 1% of CD34hi/Lin- cells are primitive hematopoietic
progenitors that produce B lymphoid and multiple myeloid progeny for up to
7 weeks in stromal cell cultures. Twenty-one percent (+/- 13%) of
CD34hi/Lin- cells also express low levels of the Thy-1 antigen and are
threefold to fourfold enriched over CD34hi/Lin- cells in primitive
hematopoietic potential as measured by long-term culture and phenotypic
analysis. One-week liquid cultures of CD34-enriched UCB progenitor cells in
the presence of interleukin (IL)- 3, IL-6, and stem cell factor (SCF)
results in a two-fold to threefold expansion of progenitors capable of
reinitiating long-term stromal cell cultures. Only the CD34hi/Thy-1+/Lin-
cell population was capable of maintaining progenitors with secondary
transfer potential in long-term stromal cell cultures and is thus
postulated to contain all of the primitive hematopoietic stem cells in UCB.
The in vivo transplantation potential of UCB was also measured. Ex vivo
manipulated UCB progenitor cells were used to engraft irradiated human
thymus fragments implanted in severe combined immunodeficiency (SCID) mice.
Thymic engraftment with >5% donor-derived cells and a normal CD4/CD8
distribution was observed in 19 of 23 tissues tested. UCB cells from in
vitro expansion cultures engrafted with efficiencies comparable to
nonexpanded cells. Similar results were obtained for UCB engraftment of
human bone fragments implanted in SCID mice. In all cases, engraftment was
achieved in competition with endogenous competitor stem cells and across
major histocompatibility barriers. Taken together, this data demonstrates
that human UCB is a rich source of multipotent hematopoietic progenitors
that can be cryopreserved, enriched by physical methods, and expanded in a
limited fashion without measurable loss of long-term culture or in vivo
engrafting potential as measured in these assays.
Volume 87,
Issue 4,
pp. 1261-1271,
02/15/1996
Copyright © 1996 by The American Society of Hematology
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