Review ArticleNanofiber technology in the ex vivo expansion of cord blood-derived hematopoietic stem cells
Graphical Abstract
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
References (105)
- et al.
Umbilical cord blood transplantation: the first 25 years and beyond
Blood
(2013) - et al.
Umbilical cord blood transplantation: pros, cons and beyond
Blood Rev
(2009) - et al.
The evolving view of the hematopoietic stem cell niche
Exp Hematol
(2017) - et al.
Hsc niche biology and hsc expansion ex vivo
Trends Mol Med
(2017) - et al.
Extracellular matrix: A dynamic microenvironment for stem cell niche
Biochim Biophys Acta Gen Subj
(2014) The stem cell niche in regenerative medicine
Cell Stem Cell
(2012)- et al.
Biomimetic electrospun nanofibrous structures for tissue engineering
Mater Today (Kidlington)
(2013) Biomimetic materials for tissue engineering
Adv Drug Deliv Rev
(2008)- et al.
Electrospinning: a fascinating fiber fabrication technique
Biotechnol Adv
(2010) - et al.
Silk-based biomaterials
Biomaterials
(2003)
Engineering ecm signals into biomaterials
Mater Today
Self-complementary oligopeptide matrices support mammalian cell attachment
Biomaterials
Electrospinning process and applications of electrospun fibers
J Electrostat
Biomimetic nanofibrous scaffolds for bone tissue engineering
Biomaterials
Bone regeneration on computer-designed nano-fibrous scaffolds
Biomaterials
Chitin and chitosan polymers: chemistry, solubility and fiber formation
Prog Polym Sci
Chitosan — a versatile semi-synthetic polymer in biomedical applications
Prog Polym Sci
Chitin and chitosan: properties and applications
Prog Polym Sci
Novel chitin and chitosan nanofibers in biomedical applications
Biotechnol Adv
Chitin and chitosan in selected biomedical applications
Prog Polym Sci
Biodegradation, biodistribution and toxicity of chitosan
Adv Drug Deliv Rev
The safety of chitosan as a pharmaceutical excipient
Regul Toxicol Pharmacol
Biomedical applications of chitin and chitosan based nanomaterials — a short review
Carbohydr Polym
Biodegradable poly (ɛ-caprolactone)–poly (ethylene glycol) copolymers as drug delivery system
Int J Pharm
Effect of stiffness of polycaprolactone (pcl) membrane on cell proliferation
Mater Sci Eng C
Poly-є-caprolactone based formulations for drug delivery and tissue engineering: a review
J Control Release
The return of a forgotten polymer — polycaprolactone in the 21st century
Prog Polym Sci
Biomimetic macroporous pcl scaffolds for ex vivo expansion of cord blood-derived cd34+ cells with feeder cells support
Macromol Biosci
Biodegradable poly (l-lactic acid)(plla) and plla-3-arm blend membranes: the use of plla-3-arm as a plasticizer
Polym Test
Improved mechanical and thermal properties of plla by solvent blending with pdla-b-peg-b-pdla
Polym Degrad Stab
Preparation of poly (l-lactic acid) microencapsulated vitamin e
Energy Procedia
Modification of porous plga microspheres by poly-l-lysine for use as tissue engineering scaffolds
Colloids Surf B Biointerfaces
Plga-based nanoparticles: a new paradigm in biomedical applications
TrAC Trends Anal Chem
Plga-based nanoparticles: an overview of biomedical applications
J Control Release
Surface-aminated electrospun nanofibers enhance adhesion and expansion of human umbilical cord blood hematopoietic stem/progenitor cells
Biomaterials
Molecular weight determination of polyethylene terephthalate
Reinforcement of polyethylene terephthalate via addition of carbon-based materials
Preparation, characterization, and applications of poly (ethylene terephthalate) nanocomposites
Antimony leaching from polyethylene terephthalate (pet) plastic used for bottled drinking water
Water Res
Functional nanofiber scaffolds with different spacers modulate adhesion and expansion of cryopreserved umbilical cord blood hematopoietic stem/progenitor cells
Exp Hematol
Methods for polyurethane and polyurethane composites, recycling and recovery: a review
React Funct Polym
Biodegradation of polyurethane: a review
Int Biodeterior Biodegradation
Long-term cytokine-free expansion of cord blood mononuclear cells in three-dimensional scaffolds
Biomaterials
The microenvironment in human myeloid malignancies: emerging concepts and therapeutic implications
Blood
Hematopoietic stem cells therapies
Curr Stem Cell Res Ther
Hematopoietic stem cell transplantation: a global perspective
JAMA
Beating the odds: factors implicated in the speed and availability of unrelated haematopoietic cell donor provision
Bone Marrow Transplant
Update on umbilical cord blood transplantation
F1000Res
Improving engraftment and immune reconstitution in umbilical cord blood transplantation
Front Immunol
Expansion of human cord blood hematopoietic stem/progenitor cells in three-dimensional nanoscaffold coated with fibronectin
Int J Hematol
Cited by (16)
Therapeutic targeting and HSC proliferation by small molecules and biologicals
2023, Advances in Protein Chemistry and Structural BiologyThe extracellular matrix of hematopoietic stem cell niches
2022, Advanced Drug Delivery ReviewsCitation Excerpt :A first indication of the sensitivity of HSPCs towards nanostructural features in their environment was provided in 2006, when Chua et al. showed that adhesion and expansion of HSPCs are enhanced on amino-functionalized polyethersulfone nanofibers in comparison to standard tissue culture plastic [454]. Thereafter, nanofibers were often used to mimic the ECM for HSPC expansion as reviewed in [486]. In the following years, it became clear that the lateral distance between adhesive ligands on the nanometer scale influences HSPC adhesion, lipid raft clustering and adhesion receptor distribution in the cells’ membrane [452,453,455].
Nanofibre and submicron fibre web formation
2022, Handbook of Nonwovens, Second EditionRebuilding the hematopoietic stem cell niche: Recent developments and future prospects
2021, Acta BiomaterialiaCitation Excerpt :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.
Disclosure statement: The authors declare no conflicts of interest.
Funding: No funding is applicable.
Acknowledgments: None.