CD34+ cell responsiveness to stromal cell–derived factor‐1α underlies rate of engraftment after peripheral blood stem cell transplantation

Oct 29, 2008Transfusion

How stem-like blood cells respond to a signaling protein affects transplant recovery speed

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Abstract

A negative correlation (r = -0.434) was observed between the chemotactic index and CD34+ cell dose in hematopoietic stem cell transplants.

Spontaneous migration of CD34+ cells ranged from 3.1% to 26.5%, while SDF-1-directed chemotaxis ranged from 11.1% to 54.9%.
Neutrophil engraftment occurred at a median of 10 days post-transplantation, with a range of 8 to 16 days.
Higher chemotactic index (CI) was associated with increased surface expression of the SDF-1 receptor CXCR4 on CD34+ cells (r = 0.8).
Patients with lower doses of CD34+ cells and higher CI experienced similar engraftment times to those with higher doses and lower CI.
Validation of CI as a prognostic factor for engraftment rates is needed in a larger patient population.

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BACKGROUND: Stromal cell-derived factor (SDF)-1, a chemokine produced in the bone marrow (BM), is essential for the homing of hematopoietic stem/progenitor cells (HSPCs) to the BM after transplantation. This study examines whether there is a correlation between the in vitro chemotaxis of CD34+ HSPC toward an SDF-1 gradient and in vivo hematopoietic engraftment.

STUDY DESIGN AND METHODS: Thirty-five patients underwent granulocyte-colony-stimulating factor HSPC collection and autologous transplant with a median dose of 7.7 (range, 3.9-41.5) x 10(6) CD34+ cells per kg body weight. The chemotactic index (CI) of CD34+ cells isolated from leukapheresis products collected from these patients was calculated as the ratio of the percentages of cells migrating toward an SDF-1 gradient to cells migrating to media alone. Expression of the SDF-1 receptor CXCR4 on CD34+ cells was measured by flow cytometry.

RESULTS: Spontaneous cell migration (range, 3.1 +/- 0.6 to 26.5 +/- 7.7%) and SDF-1-directed chemotaxis (11.1 +/- 0.7 to 54.9 +/- 8.3%) of CD34+ cells did not correlate with time to neutrophil engraftment, which occurred at a median of 10 days (range, 8-16 days). Nonparametric tests showed a negative correlation (r = -0.434) between CI and CD34+ cell dose such that neutrophil recovery occurred within the same period in patients transplanted with a lower dose of CD34+ cells but having a high CI as in those transplanted with a higher dose of CD34+ cells but having a low CI. Moreover, CI correlated (r = 0.8) with surface CXCR4 expression on CD34+ cells.

CONCLUSION: In patients transplanted with a relatively lower CD34+ cell dose who achieved fast engraftment, a higher responsiveness to SDF-1 and high CI could have compensated for the lower cell dose. However, to apply the CI as a prognostic factor of the rate of engraftment requires validation in a larger number of patients.

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CD34+ cell responsiveness to stromal cell–derived factor‐1α underlies rate of engraftment after peripheral blood stem cell transplantation

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