Medical Terminations of Pregnancy: A Viable Source of Tissue for Cell Replacement Therapy for Neurodegenerative Disorders

Abstract

"Proof-of-principle" that cell replacement therapy works for neurodegeneration has been reported, but only using donor cells collected from fetal brain tissue obtained from surgical terminations of pregnancy. Surgical terminations of pregnancy represent an increasingly limited supply of donor cells due to the tendency towards performing medical termination in much of Europe. This imposes a severe constraint on further experimental and clinical cell transplantation research. Therefore, we explore here the feasibility of using medical termination tissue as a donor source. Products of conception were retrieved from surgical terminations over the last 7 years and from medical terminations over the last 2.5 years. The number of collections that yielded fetal tissue, viable brain tissue, and identifiable brain regions (ganglionic eminence, ventral mesencephalon, and neocortex) were recorded. We studied cell viability, cell physiological properties, and differentiation potential both in vitro and following transplantation into the central nervous system of rodent models of neurodegenerative disease. Within equivalent periods, we were able to collect substantially greater numbers of fetal remains from medical than from surgical terminations of pregnancy, and the medical terminations yielded a much higher proportion of identifiable and dissectible brain tissue. Furthermore, we demonstrate that harvested cells retain the capacity to differentiate into neurons with characteristics appropriate to the region from which they are dissected. We show that, contrary to widespread assumption, medical termination of pregnancy-derived fetal brain cells represent a feasible and more readily available source of human fetal tissue for experimental cell transplantation with the potential for use in future clinical trials in human neurodegenerative disease.

Activin A directs striatal projection neuron differentiation of human pluripotent stem cells

“…Transplantation surgeries were performed as reported previously (Kelly et al, 2007(Kelly et al, , 2011 and are described in detail in the supplementary Materials and Methods. All animal experiments were performed in full compliance with the UK Animals (Scientific Procedures) Act 1986 and approved by local ethical review.…”

Neonatal Desensitization for the Study of Regenerative Medicine

“…However, PFCs are not a practical option for routine use in the clinic for several reasons. In particular, in order to implant sufficient cells of a specific striatal or dopaminergic phenotype several fetal donors are necessary for each patient (potentially up to 6 in HD, and [8][9][10][11][12] in PD) [6,7]. As storage of PFCs prior to transplantation is currently limited to a maximum of 8 days in hibernation medium [8], clinical transplantation relies on the availability of sufficient donor tissue within this time window.…”

Transplantation in HD: Are We Transplanting the Right Cells?

“…This is indicative of a foetal phenotype, rather than adult. Thus, this study showed that even after 24 days in vitro, the differentiated neurons still exhibited a foetal phenotype [7]. Apart from this preliminary analysis, little is known about the functional capacity of human-derived MSNs in vitro.…”

“…This can be straightforward depending on the method of tissue collection (i.e. medical versus surgical termination of pregnancy: MTOP and STOP, respectively), CNS tissue being more accurately dissected from MTOP-derived tissue than STOP-derived tissue due to less fragmentation of MTOP tissue, thereby enabling easier identification of different regions [7]. Thus, as a source of donor cells for transplantation, there has been a progressive move to the use of MTOP rather than the much more limited supply of STOP tissue.…”

“…We have previously used calcium imaging analysis to look at neuronal differentiation and functional cellular activity of primary human foetal-derived MSNs [7]. Exposing the in vitro differentiated neurons to various stimuli and neurotransmitter applications resulted in rises in intracellular calcium concentration.…”