Neurogenic Properties and a Clinical Relevance of Multipotent Stem Cells Derived from Cord Blood Samples Stored in the Biobanks

Abstract

Several innovative therapies with human umbilical cord blood stem cells (SCs) are currently developing to treat central nervous system (CNS) diseases. It has been shown that cord blood contains multipotent lineage-negative (LinNEG) SCs capable of neuronal differentiation. Clinically useful cord blood samples are stored in different biobanks worldwide, but the content and neurogenic properties of LinNEG cells are unknown. Here we have compared 5 major methods of blood processing: Sepax, Hetastarch, plasma depletion, Prepacyte-SC, and density gradient. We showed that Sepax-processed blood units contained 10-fold higher number of LinNEG cells after cryopreservation in comparison to all other methods. We showed in this study that multipotent SCs derived from fresh and frozen cord blood samples could be efficiently induced in defined serum-free medium toward neuronal progenitors (NF200+, Ki67+). During neuronal differentiation, the multipotent SCs underwent precise sequential changes at the molecular and cellular levels: Oct4 and Sox2 downregulation and Ngn1, NeuN, and PSD95 upregulation, similar to neurogenesis process in vivo. We expect that data presented here will be valuable for clinicians, researchers, biobanks, and patients and will contribute for better efficacy of future clinical trials in regeneration of CNS.

Experimental therapies for repair of the central nervous system: stem cells and tissue engineering

“…Interestingly, the use of this scaffold or these cells alone resulted in no significant reduction in lesion volume (Lu et al ., ). Similar results were observed by our team after intracranial transplantation of MSCs encapsulated in macroporous gelatin‐laminin cryogels (Jurga et al ., , ). These types of implants significantly reduced inflammation, glial scars, and facilitated the migration of neuroblasts into lesion sites (Jurga et al ., , , and Sarnowska, Jurga e t al .…”

“…Cells were distributed evenly within the interconnected pores with good cell‐cell interactions. We previously showed that this scaffold's structure, elasticity and biophysical properties were compatible with brain tissue extracellular matrix and that such scaffolds could be promising materials for future regenerative medical applications (Jurga et al ., , ).…”

“…Recent studies have revealed an optimal method for stem cell preparation for use in neural tissue‐engineering approaches. The current study showed better adhesion to bioscaffold of naive cord blood stem cells compared to cells differentiated into neuron‐like phenotypes prior to seeding on the biomaterial (Jurga et al ., , ). Our research group and others have focused on experimental research and development of new implantable macroporous devices for generation of artificial neural tissue to restore damaged brain tissue.…”

Direct Conversion of Cord Blood CD34+ Cells Into Neural Stem Cells by OCT4

“…Previously, human cord blood cells were reported to contain cells with neurogenic properties [13][14][15]. In order to detect whether there are any neural precursor cells in the CD34+ fraction of CB, we cultured CB CD34+ cells directly on laminin-coated tissue culture plates in ReNcell medium in the presence of human EGF and bFGF, which is a well established and standard culture condition for human neural stem cells (Millipore).…”

An Overview on Human Umbilical Cord Blood Stem Cell-Based Alternative In Vitro Models for Developmental Neurotoxicity Assessment

“…In addition, hUCB-MSCs have also been extensively studied for neurogenic potentials [105,81,[108][109][110][111]. Recently, Zhang and colleagues [76] used condition mediumconstituted olfactory ensheathing cells for the differentiation of mesenchymal stem cells into neuronal cells.…”