Review Article
Nanofiber technology in the ex vivo expansion of cord blood-derived hematopoietic stem cells

https://doi.org/10.1016/j.nano.2018.04.017Get rights and content

Abstract

Umbilical cord blood (CB) can be used as an alternative source of hematopoietic stem cells (HSCs) for transplantation in hematological and non-hematological disorders. Despite several recognized advantages the limited cell number in CB one unit still restricts its clinical use. The success of transplantation greatly depends on the levels of total nucleated cell and CD34+ cell counts. Thus, many ex vivo strategies have been developed within the last decade in order to solve this obstacle, with more or less success, mainly determined by the degree of difficulty related with maintaining HSCs self-renewal and stemness properties after long-term expansion. Different research groups have developed very promising and diverse CB-derived HSC expansion strategies using nanofiber scaffolds. Here we review the state-of-the-art of nanofiber technology-based CB-derived HSC expansion.

Section snippets

Bone marrow hematopoietic stem cell niche architecture

Efficient ex vivo production and expansion of HSCs are essential to recognize the full clinical potential of HSCs, HSC-derived cells and other BM niche cells. To achieve that goal ex vivo culture systems that can recapitulate the complexities of the microenvironment within the BM and hematopoietic niches are essential.10

Hematopoiesis is a lifelong process of producing blood cells from HSCs. Hematopoiesis in the BM relies on the association between HSCs and adjacent microenvironment. HSCs

Nanofiber and materials

The 3D scaffolding is a complex process ideally including the following criteria: (1) promotion of cell-substrate interactions, (2) no cytotoxicity, (3) controlled biodegradation rate of the material, (4) stimulation of none or minimal immune response or inflammation, (5) compatibility with physiological conditions, (6) easy to scale-up production and processing, (7) easy transplantation into the human body.19 Except for the criteria related with scaffold architecture and design, every

Fabrication

One of the main challenges in the field of TE is the design and fabrication of 3D scaffolds that mimic the architecture of human tissues at the nanometer size, especially in the case of BM if one considers the high complexity of having cellular components, microenvironment and the existence of a vascular as well an osteogenic niche.

Several processing techniques have been developed to fabricate nanofibers for 3D scaffolding; we will discuss three: phase separation,36 self-assembly37, 38 and

Expansion of cord blood-derived hematopoietic stem cells using nanofibers

We have compiled in Table 1, Table 2 a series of studies relating to expansion of CB-derived HSCs using different nanofiber materials that we would like to highlight among the recent literature.

Outlook on HSC expansion and BM mimicry

Essentially, the problems in developing a TE strategy for ex vivo expansion of HSCs are the (i) biological complexity, (ii) difficult accessibility and (iii) challenging geometry of the native BM niche. Recent evidence leads to the suggestion that the complexity of the HSC niche is not only affected by hematological disease but actively influences disease progression and even development.99 This is very interesting and must not only change our perception of the BM niche but also impact the

Conclusion

Nanofiber materials of different nature and sizes have been used to design scaffolds of different architectures with the major goal of mimicking the native BM niche.

Here we placed into perspective how nanofiber characteristics might influence cell behavior, by the nature of the material used (natural/synthetic polymers), the physicochemical properties such as biocompatibility, porosity, pore size, interpore connectivity, biodegradability, surface-modification, surface-to-volume ratio, as well

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      Among them, electrospinning has been of major interest owing to its ability to produce NFs similar to the fibrous structure of ECM, the ease of controlling their diameter, its applicability for a wide range of materials and cost-effectiveness. Natural polymers, e.g. collagen, silk, gelatin and elastin or synthetic polymers such as polycaprolactone (PCL), poly(glycolic acid) (PGA), poly(L-lactic acid) (PLLA), poly(lactic-co-glycolic acid) (PLGA) and polyurethanes (PU) have been used in NF fabrication [98] but they all have advantages and disadvantages. While natural polymers, in general, have a good biocompatibility and hydrophilicity, they suffer from weak mechanical properties and low processability.

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    Disclosure statement: The authors declare no conflicts of interest.

    Funding: No funding is applicable.

    Acknowledgments: None.

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