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Umbilical Cord Blood Stem Cell Showdown Suggests Fresh is Best!

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Review of “Functional Integrity and Gene Expression Profiles of Human Cord Blood‐Derived Hematopoietic Stem and Progenitor Cells Generated In Vitro” from STEM CELLS Translational Medicine by Stuart P. Atkinson

While umbilical cord blood (UCB) transplantation represents the first‐line therapy for some hematological conditions in pediatric patients, relatively low absolute numbers of hematopoietic stem and progenitor cells (HSCs and HPCs) [1] may lead to poorer outcomes in adult patients [2]. The ex vivo‐expansion of HSCs and HPCs represent a potentially exciting means to improve treatment outcomes, although doubts remain regarding the equivalence of in vitro expanded and freshly isolated cells.

Researchers from the laboratory of Hector Mayani  (IMSS, Mexico City, Mexico) sought to answer this question by comparing HSCs, myeloid progenitor cells (MPCs), and erythroid progenitor cells (EPCs) obtained directly from fresh UCB units with those generated from fresh HSCs in vitro. Interestingly, their new STEM CELLS Translational Medicine article suggests that in vitro‐generated cells present with functional and genetic differences that may have significant biologic and clinical implications [3]. So, in an umbilical cord blood stem cell showdown, is fresh best?

Comparisons made by Dircio‐Maldonado et al. suggested that while all three cell populations displayed a similar proliferation capacity, their expansion potentials differed. HSCs generated in vitro displayed lower numbers of long‐term culture‐initiating cells (LT-ICs) and a myeloid differentiation bias when compared to HSCs from fresh UCB units. Furthermore, both HSCs and HPCs exhibited a limited potential for expansion. KEGG and GO analysis of global gene expression changes linked alterations to HSCs/HPCs to increased JAK‐STAT, PI3K‐AKT, NFkB, and HIF‐1 signaling and the more prominent appearance of processes such as cell cycle, apoptosis, and myeloid differentiation in in vitro generated cells.

While the authors suggest that the gene expression changes correlate well with the functional alterations observed in in vitro generated cells when compared to cells derived from fresh UCB units, they also urge caution. The use of a single ex vivo culture strategy did not permit the analysis of functional integrity and gene expression profiles of the same cell populations generated under different culture conditions. However, the authors do hope that their results, which indicate that fresh is best for HSCs and HPCs from UCB, will contribute to the clinical application of UCB expansion and transplantation.

For more on the differences between umbilical cord blood stem cells in vivo and in vitro, stay tuned to the Stem Cells Portal

References

  1. Stanevsky A, Goldstein G, and Nagler A, Umbilical cord blood transplantation: Pros, cons and beyond. Blood Reviews 2009;23:199-204.
  2. Ooi J, Cord blood transplantation in adults. Bone Marrow Transplantation 2009;44:661.
  3. Dircio-Maldonado R, Flores-Guzman P, Corral-Navarro J, et al., Functional Integrity and Gene Expression Profiles of Human Cord Blood-Derived Hematopoietic Stem and Progenitor Cells Generated In Vitro. STEM CELLS Translational Medicine 2018;7:602-614.