Regenerative Medicine (RM) is directed at
the regeneration of mulfunctioning tissues and organs. This program is actively
involved in the introduction of novel research lines investigating the therapeutic potential of mesenchymal
stem cells (MSC). Pluripotent mesenchymal stem cells (MSCs) are present in a
variety of tissues during human development, and in adults they are prevalent
in the bone marrow where they have been isolated, expanded in culture and
differentiated. They are thought to be the critical in the production of
progenitors with the potential to generate a spectrum of tissues including
bone, cartilage, fat and the marrow stroma itself.
Our knowledge about the
complex, multistep and multifactorial molecular mechanisms underlying MSC
differentiation is currently insufficient to generate “tailor-made MSC” for
disease-specific application. The potential for the therapeutic use of MSC has
been recently investigated in several diverse settings (i) osteogenesis
imperfecta; (ii) Hurler syndrome and (iii) graft-versus-host disease.
However, current problems in the use of MSC
for regenerative medicine include (a) lack of multipotency after in vitro
culture, (b) poor survival of cells when transplanted in vivo, (c) optimal age
of donors and source of isolated MSC and (d) poor proliferation of MSC in vitro
resulting in minimal expansion.
This program aims at understanding the
molecular and cellular mechanisms underlying the survival, proliferation and
differentiation of MSC. By ex-vivo manipulation of these cells it should be
possible to increase their therapeutic potential and eventually generate
“tailor-made MSCs” for application to specific pediatric diseases.
General Aims
1. To understand the molecular mechanisms
regulating the expansion and differentiation of MSC. This involves analysis of
the intracellular signaling pathways and epigenetic regulatory mechanisms with
the aim of improving the survival, expansion and differentiation of MSC in vivo.
2. To evaluate the functional consequences
of “aged” versus “young” MSC, as well as stem cell sources (bone marrow, fat,
Wharton’s jelly) for therapeutic use.
3. To develop novel (molecular) therapies
enabling functional modulation of MSC ex-vivo and allowing novel, tailor-made
therapeutic strategies for orthopedic, metabolic and immune diseases.
4. Participate in state-of-the-art clinical
trials utilizing MSC for treatment of pediatric disease.