Comparison of Hematopoietic Activities of Human Bone Marrow and Umbilical Cord Blood CD34 Positive and Negative Cells

Kim, Dong Ku; Fujiki, Yutaka; Fukushima, Takashi; Ema, Hideo; Shibuya, Akira; Nakauchi, Hiromitsu

doi:10.1002/stem.170286

Cited by 69 publications

(50 citation statements)

References 37 publications

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“…Especially after transfer of CD34 + cells from UCB, the main cell lineage recovering in the NOD/SCID mice has been reported to be of B cells. [24][25][26][27][28][29] Similarly, we found that after relatively low doses of UCB CD34 + cells 81-95% of the engrafted cells were of B cell origin. At these doses only very low engraftment was found with BM or mPB CD34 + cells, not allowing reliable evaluation of specific cell lineages by flow cytometry.…”

Section: Discussionmentioning

confidence: 85%

Similar myeloid recovery despite superior overall engraftment in NOD/SCID mice after transplantation of human CD34+ cells from umbilical cord blood as compared to adult sources

Noort

Wilpshaar

Hertogh

et al. 2001

Bone Marrow Transplant

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Summary:Umbilical cord blood (UCB), bone marrow (BM) and mobilized peripheral blood (mPB) are used as sources of hematopoietic stem cells for transplantation. The NOD/SCID mouse model was used to compare the lineage-specific repopulating potential of CD34 + cells derived from these sources. Six to 8 weeks after transplantation, blood, BM, spleen, liver and thymus, were harvested, and analyzed by flow cytometry using CD34, CD45, myeloid, and lymphoid lineage-specific antibodies. Fifty percent engraftment of human cells in bone marrow of mice was estimated to be reached with 0.55 × 10 6 CD34 + UCB cells or with 7.9 × 10 6 CD34 + cells from adult sources, illustrating a 10-fold superiority of UCB CD34 + cells to engraft NOD/SCID mice. Lineagespecific characterization of engrafted human cells showed that the high engraftment potential of CD34 + cells from UCB was due to a preferential B cell development (2-81%). In contrast, comparable percentages of myeloid cells were found following transplantation of CD34 + cells from UCB, BM and mPB (1-38%), and occurred at significant levels only at relatively high doses. Since the CD34 content of UCB transplants is usually at least one log lower than of transplant from adult sources, these results correspond to the clinical findings with UCB transplantation showing a relatively high overall engraftment, but delayed myeloid recovery. blood (mPB), and umbilical cord blood (UCB). The HPC source used for an individual patient may depend on the availability of the graft, the disease and the age of the patient, and the risks of complications after the transplant. For instance, transplantation with a mPB graft has been shown to result in more rapid recovery of granulocytes and platelets than BM transplantation, but is associated with a higher incidence of chronic graft-versus-host disease (GVHD). [2][3][4] In contrast, UCB transplantations have been reported to be accompanied by a relatively low incidence and severity of GVHD, but are associated with delayed hematopoietic recovery. 5,6 In part, the relatively slow speed of engraftment following UCB transplantation is thought to be due to the limited numbers of HSC that can be transplanted. The limited volume of UCB that can be obtained from a single harvest results in a graft usually containing at least one log fewer CD34 + cells than a BM graft. 6,7 However, qualitative differences in the CD34 + cell fraction from the various sources of HSC may also influence the recovery after transplantation. [8][9][10][11][12][13][14] The CD34 + CD38 Ϫ cell population from UCB, containing the most primitive cells essential for engraftment, showed a higher cloning efficiency, proliferated more rapidly in response to cytokine stimulation and generated more progeny than the CD34 + CD38 Ϫ cells from BM counterparts. 8 In part, the higher proliferative potential of primitive cells from UCB may be ascribed to their ability to leave the dormant state more rapidly than their BM counterparts. 14 In vivo functional differences among human stem cells from s...

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Section: Discussionmentioning

confidence: 85%

Similar myeloid recovery despite superior overall engraftment in NOD/SCID mice after transplantation of human CD34+ cells from umbilical cord blood as compared to adult sources

Noort

Wilpshaar

Hertogh

et al. 2001

Bone Marrow Transplant

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“…Separation of these cells is particularly difficult not only because of the very low percentage of stem cells present but also because of variation in expression levels of the stem cell marker, CD34 (29,30). Preliminary results suggest that optimal magnetic labeling of CD34 1 cells from umbilical cord blood requires at least 15 ml/10 6 cells a-PE-MACS when the cells are saturated with a-CD34-PE (unpublished results).…”

Section: Discussionmentioning

confidence: 95%

Cell tracking velocimetry as a tool for defining saturation binding of magnetically conjugated antibodies

et al. 2005

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Background: Continuous flow immunomagnetic separation is an attractive alternative to current batch mode immunomagnetic separation methods because it is capable of high sorting speeds at mild cell conditions, and grants the operator better control of separation process. The control of the separation is dependent on knowledge of the amount of magnetic label attached to the cell (magnetic labeling intensity), however. Determination of the magnetic labeling is accomplished by measuring cell magnetophoretic mobility using a newly developed technique of Cell Tracking Velocimetry (CTV). Methods: Flow cytometry was used to define the antibody binding characteristics of a fluorescently tagged primary antibody. Subsequently, CTV was used to measure antibody‐binding characteristics of a magnetically tagged secondary antibody. Results: The results of this study show that CTV is capable of providing valuable information concerning the cell labeling by magnetically tagged antibodies. It was demonstrated that the magnetically conjugated antibody binding curve exhibits the same exponential increase to saturation characteristics as that seen with the fluorescently tagged antibody. Further, it was shown that the intensity of the secondary magnetic labeling is directly proportional to the intensity of the primary fluorescent label. Conclusions: CTV is an accurate tool for evaluation of magnetically conjugated antibodies. The ability to determine the intensity of magnetic labeling is necessary for the development of continuous flow immunomagnetic separations based on cell magnetophoresis. © 2005 Wiley‐Liss, Inc.

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“…[1][2][3][4][5][6][7][8][9][10][11]16 A number of clonal tracking studies using retro-or lenti-viral vector have shown that CB-derived CD34 þ cells are a heterogeneous population and contain ST-and LT-repopulating SRCs. 16,[18][19][20][21] Guenechea et al 18 revealed that the type of repopulation in NOD/SCID mice that receive transplants of retrovirally transduced CB-derived HSCs is generally oligoclonal with an extensive variability in the life span and proliferative capacity of individual SRCs.…”

Section: Discussionmentioning

confidence: 99%

“…A number of studies have revealed that the severe combined immunodeficiency (SCID)-repopulating cell (SRC) activity reside in CD34-positive (CD34 þ ) cell factions derived from bone marrow (BM), cord blood (CB), and peripheral blood. [1][2][3][4][5][6] Recently, we successfully identified human CB-derived CD34-negative (CD34 À ) SRCs with extensive lymphoid and myeloid repopulating ability using the intra-bone marrow injection (IBMI) method. 7 Functional studies revealed that these CD34 À SRCs have different HSC characteristics from earlier-reported CD34 þ SRCs.…”

Section: Introductionmentioning

confidence: 99%

In vivo dynamics of human cord blood-derived CD34− SCID-repopulating cells using intra-bone marrow injection

et al. 2009

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The identification of human CD34-negative (CD34 À ) hematopoietic stem cells (HSCs) provides a new concept for the hierarchy in the human HSC compartment. This study investigated the long-term repopulating capacity and redistribution kinetics of human cord blood-derived CD34 À severe combined immunodeficiency (SCID)-repopulating cells (SRCs) and compared them with those of CD34 þ CD38 þ and CD34 þ CD38 À SRCs using the intra-bone marrow injection (IBMI) to clarify the characteristics of CD34 À SRCs. On the basis of the limiting dilution analyses data, estimated numbers of CD34 þ CD38 þ , CD34 þ CD38 À , and CD34 À SRCs were transplanted to NOD/SCID mice by IBMI. The human cell repopulation at the site of injection and the other bones were serially investigated. Interestingly, CD34 þ CD38 þ , CD34 þ CD38 À , and CD34 À SRCs began to migrate to other bones 2 and 5 weeks after the transplantation, respectively. Accordingly, the initiation of migration seemed to differ between the CD34 þ and CD34 À SRCs. In addition, CD34 þ CD38 þ SRCs only sustained a shortterm repopulation. However, both CD34 þ CD38 À and CD34 À SRCs had longer-term repopulation capacity. Taken together, these findings showed that CD34 À SRCs show different in vivo kinetics, thus suggesting that the identified CD34 À SRCs are a distinct class of primitive HSCs in comparison to the CD34 þ CD38 þ and CD34 þ CD38 À SRCs.

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Comparison of Hematopoietic Activities of Human Bone Marrow and Umbilical Cord Blood CD34 Positive and Negative Cells

Abstract: ABSTRACT

Cited by 69 publications

References 37 publications

Similar myeloid recovery despite superior overall engraftment in NOD/SCID mice after transplantation of human CD34+ cells from umbilical cord blood as compared to adult sources

Similar myeloid recovery despite superior overall engraftment in NOD/SCID mice after transplantation of human CD34+ cells from umbilical cord blood as compared to adult sources

Cell tracking velocimetry as a tool for defining saturation binding of magnetically conjugated antibodies

In vivo dynamics of human cord blood-derived CD34− SCID-repopulating cells using intra-bone marrow injection

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