Obtención, expansión y caracterización de células precursoras de piel humana (Skin-derived Precursor Cells, SkPs) en relación a la edad y área donante
Author
Gago López, NuriaEntity
UAM. Departamento de Biología MolecularDate
2009-06-19Subjects
Piel-Tesis doctorales; Biología y Biomedicina / BiologíaNote
Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 19-06-2009Abstract
A major unanswered question in autologous cell therapy is the appropriate timing for cell
isolation. Many of the putative target diseases arise with old age and previous evidence,
mainly from animal models suggests that the stem/progenitor cell pool decreases steadily
with age. Human skin is an easily accesible reservoir of adult stem cells, which makes it an
ideal source of autologous cells for transplant. Several groups have now reported on the
existence of neural crest-derived precursor cells in the dermis. These skin-derived precursor
(SKP) cells are multipotent, giving rise in a clonal way to both neural and mesodermal
progenies (neurons, glia, smooth muscle cells and adipocytes). However they seem to
generate mostly peripheral neurons and Schwann cells. Murine SKPs have already been
succesfully used in models of spinal cord injury and as a vehicle for the treatment of gliomas.
Our intention was to characterize human SKPs in order to facilitate their use in clinical
protocols, with four main objectives: (i) to establish the best donor area for use of these cells
in clinical protocols, since preliminary evidence showed important differences in cell
extraction and differentiation potential; (ii) to determine donor age influence on SKP
abundance and differentiation potential; (iii) to determine best culture conditions to expand
the cells sufficiently for their clinical use while maintaining their stem cell properties; and (iv)
to phenotypically characterize cellular subset in the primary cultures that gives rise to neural
progeny, since present isolation of SKPs permits coculture of terminally differentiated cells
that do not contribute to neural specification.
In this Thesis we show an analysis of human SKP abundance and in vitro differentiation
potential, by using SKPs isolated from four distinct anatomic sites (abdomen, breast, foreskin
and scalp) from >100 healthy subjects aged 8 months-85 years. Human SKP abundance and
differentiation potential are similar in all areas but decrease sharply with age, being
extremely difficult to isolate, expand and differentiate when obtained from the elderly. Our
data suggest preserving human SKP cell banks early in life would be desirable for use in
clinical protocols in the aging population. We further show how donor age is also important
when methylcellulose is not added to the culture medium. Finally, we present some
preliminary results on the purification of human SKPs by cell sorting, the initial isolation and
characterization of monkey SKPs and a thorough characterization of dental pulp stem cells in omparison with mesenchymal stromal cells to be used in dental implants.
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