Expansion of human hematopoietic stem cells for transplantation: trends and perspectives

Abstract

Umbilical cord blood transplantation is clinically limited by its low progenitor cell content. Ex vivo expansion has become an alternative to increase the cell dose available for transplants. Expansion has been evaluated in several ways such as static cultures combining growth factors or mimicking the natural microenvironment using co-culture systems. However, static cultures have a small volume capacity and therefore large-scale expansion has been addressed using bioreactors. These and other biotechnological approaches for the expansion of hematopoietic progenitors and their utility to study several aspects of hematopoietic stem cell biology are discussed here.

Process challenges relating to hematopoietic stem cell cultivation in bioreactors

“…The media is the nutritional source for the HSCs and a combination of human/animal serum with a cytokine cocktail [1]. To make allowances for the complexity of the microenvironment for hematopoiesis and the limitations in the knowledge of these complex interactions, serum is added to ensure that the ex vivo conditions mimic the in vivo conditions.…”

“…The serum provides essential nutrients, hormones and growth factors and protects cells from potential damage in the culture environment [3]. However, despite these positive effects, the addition of serum has some disadvantages: unknown composition, which increases the uncontrolled variability of the experiment [2]; possible inhibitory factors [3], which could result in immunological rejection of cells when transplanted [1]. More recently a serum-free media has been used to overcome these disadvantages [2].…”

Hematopoietic stem cells from peripheral blood the perspective of non-mobilized peripheral blood

“…Results from pilot clinical trials of transplants using expanded UCB-HSC have shown no adverse effects in the patients. However, more clinical trials must be conducted using expanded HSC for guarantying the safety [82]. Very recently, Delaney et al (2010) claimed that when cord blood progenitors expanded ex vivo in the presence of Notch ligand we infused in a clinical setting after a myeloablative preparative regimen for stem cell transplantation, the time to neutrophil recovery was substantially shortened.…”

Agitation increases expansion of cord blood hematopoietic cells and promotes their differentiation into myeloid lineage

“…Then, because of its availability, ease of gathering and low likelihood of graft versus host diseases, UCB-hematopoietic stem cells (UCB-HSCs) have been broadly applied to treat hematologic disorders, immune deficiency diseases and genetic diseases (Almici et al 1995;Andrade-Zaldívar et al 2008;Kowalczyk et al 2011). Regardless of all advantages mentioned, low count of stem cells per each unit of UCB restricts its application especially for adults (Andrade-Zaldívar et al 2008;Cabrita et al 2003). Consequently, employing methods for ex-vivo expansion of stem cells seems essential (AndradeZaldívar et al 2008;Kowalczyk et al 2011;Broxmeyer et al 2006).…”