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Principles of REGENERATIVE MEDICINE Prof. Paolo Macchiarini. Regenerative Medicine is the process of creating living, functional tissues to repair or replace tissue or organ function lost due to age, disease, damage, or congenital defects. the shortage of organs available for donation
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Principles of REGENERATIVE MEDICINE Prof. Paolo Macchiarini
Regenerative Medicine is the process of creating living, functional tissues to repair or replace tissue or organ function lost due to age, disease, damage, or congenital defects. • the shortage of organs available for donation • organ transplant rejection
Bioengineering Medicine Chemical Engineering Developmental Biology Molecular Biology Regenerative Medicine MaterialsScience Biochemistry Drug Delivery Genomics Proteomics Physiology Nanotechnology
Regenerative Medicine in vitro approach: therapy studied inside the laboratory implanted in the body in vivo approach: studies performed inside the living body clinical use
Regenerative Medicine Cell Therapy Tissue Engineering
Cell Therapy • There are two ideas behind the use of cells as a medical treatment: • to provide a source of missing cells • to manipulate cells to produce a missing substance
Cell Therapy • Transplated cells: • Mature, functional cells • Modified human cells • Transdifferentiated own patient’s cells • Non-human cells (xenotransplantation) • Stem cells (autologous or allogeneic)
Stem Cells Self-renewing, undifferentiated, multipotent cells
Stem Cells Embryonic Stem Cells Adult Stem Cells Derived from embryonic blastocysts Pluripotent Residue within adult tissues Multipotent
Cell therapy challenges • Directing cells to the proper place • Integrating cells with the patient’s own tissue • Overcoming the phenomenon of tissue rejection
Tissue Engineering Tissue Engineering is “an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ“ (Langer R, Vacanti JP. Science 1993; 260: 920)
Tissue Engineering approach in vitro cell expansion biopsy Scaffold seeding Static culture Implantation Dynamic culture
Autologous cells Primary cells Allogeneic cells Secondary cells Cell sources Xenogenic cells Syngenic or isogenic cells Stem cells
Scaffold • Allow cell attachment and migration • Deliver and retain cells and biochemical factors • Enable diffusion of vital cell nutrients and expressed products • Exert certain mechanical and biological influences to modify cell behaviour
Biomaterials • easy and reproducible manufacture Synthetic • biocompatibility • non-immunogenicity Natural • suitable resorption rates
Synthetic biomaterials Polylactic acid (PLA) Polyglycolic acid (PGA) Poly(e) caprolactone (PCL)
Natural biomaterials Collagen Fibrin Chitosan Hyaluronic acid (glycosaminglycans) Extracellular matrix
Challenges To obtain the suitable scaffold, to control the spatial distribution of cells, the proper combination of culture conditions/growth factors to allow the construction of a vital vascularized substitute with natural tissue anatomic, mechanical and antiinflammatory functions