Research is presently being conducted on several different types of tissues and organs, including: Skin Cartilage Blood Vessels Bone Muscle Nerves Liver Kidney etc. etc. etc. Tissue Engineering Tissue Engineering is the in vitro development (growth) of tissues or organs to replace or support the function of defective or injured body parts.
Tissue Engineering. Tissue Engineering is the in vitro development (growth) of tissues or organs to replace or support the function of defective or injured body parts. Research is presently being conducted on several different types of tissues and organs, including: Skin Cartilage - PowerPoint PPT Presentation
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Research is presently being conducted on several different types of tissues and organs, including:
Skin Cartilage Blood Vessels Bone Muscle Nerves Liver Kidney etc. etc. etc.
Tissue EngineeringTissue Engineering is the in vitro development (growth) of tissues or organs to replace or support the function of defective or injured body parts.
Tissue Organization
Before a tissue can be developed in vitro, first we must understand how tissues are organized. The basic tenant here is that:
“all tissues are comprised ofseveral levels of structural hierarchy”
These structural levels exist from the macroscopic level (centimeter range) all the way down the molecular level (nanometer range)
there can be as many as 7-10 distinct levels of structural organization in some tissues or organs
Organization of the Tendon
Organization of the Kidney
Cellular CommunicationsSoluble Signals:
small proteins (15-20 kDa) which are chemically stable with long half-lives (unless specifically degraded)
» growth factors, steroids, hormones, cytokines, chemokines bind to membrane receptors usually with high affinity (low binding constants:
10-100 pM) can diffusion long distances
Cellular CommunicationsCell-to-Cell Contact:
some membrane receptors are adhesive molecules» adherent junctions and desmosomes
other serve to create junctions between adjacent cells allowing for direct cytoplasmic communication
» gap junctions» 1.5-2 nm diameter and only allow transport of small
molecules ~1 kDa
Cellular CommunicationsCell-ECM Interactions:
ECM is multifunctional and also provides a substrate that cells can communicate
since cells synthesize the ECM, they can modify the ECM to elicit specific cellular responses
several specialized receptors that allow for cell-ECM interactions» integrins, CD44, etc.» also a mechanism by with cells respond to external stimuli (“mechanical
» nutrients, amino acids, vitamins, minerals, growth factors, etc.
Cell SourcesSince the ultimate goal of tissue engineering is to develop replacement tissue (or organs) for individuals, the use of autologous cells would avoid any potential immunological complications.
Various classifications of cells used in tissue engineering applications: primary cells
» differentiated cells harvested from the patient (tissue biopsy)» low cellular yield (can only harvest so much)» potential age-related problems
passaged cells» serial expansion of primary cells (can increase population by 100-1000X)» tendency to either lose potency or de-differentiate with too many passages
stem cells» undifferentiated cells» self-renewal capability (unlimited?)» can differentiate into functional cell types» very rare
Stem CellsStem cells naturally exist in some tissues (especially those that rapidly proliferate or remodel) and are present in the circulation.
There are two predominant lineages of stem cells: mesenchymal
» give rise to connective tissues (bone, cartilage, etc.)» although found in some tissues, typically isolated from bone marrow
hematopoietic» give rise to blood cells and lymphocytes» isolated from bone marrow, blood (umbilical cord)
Stem cells are rare; bone marrow typically has: a single mesenchymal stem cell for every 1,000,000 myeloid cells a single hematopoietic stem cell for every 100,000 myeloid cells
Stem Cells (Mesenchymal)
Stem Cells (Hematopoietic)
Colony-Forming Units (CFUs)
Bioreactorsa) Spinner Flask:
semi-controlled fluid shear can produce turbulent eddies which
could be detrimental
b) Rotating Wall low shear stresses, high mass transfer
rate can balance forces to stimulate “zero
gravity”
c) Hollow Fibre used to enhance mass transfer during
the culture of highly metabolic cells
d) Perfusion media flows directly through construct
e) Controlled Mechanics to apply physiological forces during