tissue engineering and stem cell by regenerative medicine.pptx badal 2014
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Pradeep KumarM.Sc. Biotechnology
Tissue engineering using stem cellas regenerative medicine
Introduction
Tissue engineering is an interdisciplinary field that applies the
principles of engineering and the life sciences toward the
development of biological substitutes that restore, maintain, or
improve tissue function.
In mid 1960s, artificial skin was being used.
In the, early 1970s, there were concerted efforts to treat artificialsurfaces to be used in implants in ways that would enable themto avoid causing blood coagulation, by applying special heparincomplex coatings.
In the late 1970s, researchers experimented with collagen basedartificial skin for use in oral mucosa injuries.
In the, 1980s, R&D in tissue engineering and biomaterials tookoff. As part of this interest, several biomedical engineeringdepartments were established at major universities around theworld.
o In 1981, a skin equivalent consisting of a silicon covers a sponge
of porous collagen cross linked with chondriotin was used
successfully to treat severe burn.
o The term “tissue engineering” was first used by Eugene Bell of
MIT in 1984, and later was also referred to extensively by
Wolter and Meyer in 1984.
o Interpore's Pro-Osteon coral-derived bone graft material was
introduced in 1993.
o In 1996, Integra's Artificial Skin was approved for as an in
vivo, nonbiological tissue regeneration product.
o 1998 the general and plastic surgery approval of ‘Apligraf’,
human skin equivalent for the treatment of venous leg ulcers.
Prerequisite for tissue engineering
• Growth of cell in three dimensional systems
• Delivery systems for protein therapeutics
• Cell cultivation methods for culturing recalcitrant cells
• Transgenic protein expression in transplantable cells
• Vehicles for delivering transplantable cells
• Avoiding immunogenicity in transplantation systems
• Development of markers for tracking transplanted cell
• Developing in vivo and ex vivo biosensors for monitoring cell behaviour during tissueproduction.
• Tissue engineering and cell therapy
aims to provide therapies for diseases
such as Neurodegenerative diseases,
Cardiovascular disease, Diabetes, and
Musculoskeletal disease.
• It is also used in regeneration of the
lost organs due to accident.
STEM CELLS
1. Blood
2. Skin
3. Pancreas
4. Heart
5. Liver
6. Muscle
7. Brain
Why stem cell used as regenerative
medicine
• Stem cells are unspecialized cells
that can self-renew indefinitely
and that can also differentiate
into more mature cells with
specialized functions.
• Self-renewal – the ability to go
through numerous cycles of cell
division while maintaining the
undifferentiated state.
Sir John B. GurdonShinya Yamanaka
The Nobel Prize in Physiology or Medicine 2012 was awarded jointly
to Sir John B. Gurdon and Shinya Yamanaka "for the discovery that
mature cells can be reprogrammed to become pluripotent"
Hematopoietic stem cells
Mesenchymal stem cell
Tissue specific stem cell
Embryonic stem cell
Major Source of stem cell
common myeloid
progenitors
common lymphoid progenitors
In an individual Formation of
all blood cell form embryonic to
adult phase of life through
Hematopoiesis process.
All blood cells arise from a type
of cell called the hematopoietic stem
cell (HSC).
• Failure of Hematopoiesis leads todevelopment of leukemia.
• Transplants of hematopoietic stem cellscould replace a cancerous blood system inhumans and hence cure leukemia.
• Bollywood celebrity Lisa Ray to undergostem cell transplant for blood cancer.
• Mesenchymal stem / multipotent stromal cells (MSCs)
are capable of differentiating into multiple types of
connective tissues like bone, cartilage, muscle neuron.
• MSCs have potential utility for treating a variety of
diseases and disorders, including graft versus host
disease, organ transplantation, cardiovascular disease,
brain and spinal cord injury, lung, liver and kidney
diseases, and skeletal injuries.
• Stem cell are throught to exist in many other niches
throught the body apart from the bone marrow but are
perhaps best studied in the brain and the skin.
• NSCs as they become to be known, could be isolated
from these neurospheres and selectively differentiated
into the three main cells of the brain neurons, glial cells
and oligodendrocytes.
Germ-line
Tissue-specific stem
cells:
• ESCs have the potential to grow indefinitely and candifferentiate into all cell types of the adult.
• ESCs are found in the inner cell mass of the humanblastocyst(64 cell), an early stage of the developing embryolasting from the 4th to 7th day after fertilization.
• ESCs have the advantage over other cell types of being trulypluripotent, i.e., ESCs have the potential to develop into allthree germ layers.
Stem cell therapies
• Cardiovascular disease causes40% of all death in the unitedstates each year.
• Many treatments, includingpharmacological, lifestyle,and surgical, are available forcoronary heart disease, but asyet there is no treatment otherthan transplantation that cancause repair of damaged heartmuscle.
Alternatives to transplant are being considered, including
Xenotransplantation and artificial mechanical hearts but new
treatments that can repair or replace damaged tissue in the heart
are desperately needed.
• Stem cell research into the
generation of bone and
cartilage is linked
intrinsically to tissue
engineering.
• MSCs can differentiate into
both osteoblasts and
chondrocytes, that a
combination of MSCs and a
suitable scaffold can rectify
bone injuries in animals.
Cell therapy Neurodegenerative disease
• Parkinson’s
• Huntington’s
• Alzheimer’s
• Amyotrophic lateral sclerosis (ALS)
• Spinal cord injury
• Multiple sclerosis (MS)
Cont…Approaches to Stem Cell Therapies For Neurological Disease
1. Transplantation of neural stem cells
Donor: fetal brain
• Cell therapies that replace pancreatic β-cells in type I diabetesand augment their effect in type II diabetes would lighten theeconomical and social burden considerably.
• The insulin producing cells obtained in such experiments maybe more closely related to nerve cells than to endocrine cells.
• The most recent study at the time of writing claimed thateuglycemia was restored in 30% of streptozotocin treated miceimplanted with ESC derived β-cells.
• Pancreatic tissue produced from ESCs are better defined, theapplication of ESCs for clinical correction of type I diabetesremains a distant prospect.
Recent Invention
• Technion researchers have
succeeded in constructing a
three-dimensional
polymeric scaffold array
with pancreatic islets
surrounded by a vascular
network, reports the
scientific journal PLoSONE. ”July ,15th, 2012”
Growing a nose on a forehead or an ear on an arm is a revolutionary approach tosurgical reconstruction.
This patient suffered irreparabledamage to his nose from a caraccident and subsequentinfection. Now surgeons aregrowing a replacement on hisforehead.
One of the most complicated ear constructions in theU.S., involves removing cartilage from the rib cage toform a new ear, which is then placed under the skin ofthe forearm to grow.
• Dr. Harald Ott and his
team grew a kidney by
using an experimental
technique that has
previously been used to
create working hearts,
lungs and livers.
• Their work was published
on Sunday, “14th April,
2013 in “Nature Medicine”
3-D Printer Makes A Bionic Ear
• Their work was published on
thursday “ 2, May, 2013 in
“Nano Letters”.
Tissue engineering provides long term and much safer
solution than other options.
The traditional transplantation complications are
minimized.
The donar can be patients himself or herself.
The need for donar tissue is minimal.
Immuno suppression problem can be minimized.
The presence of residual foreign material can be
minimized.
Cell isolation and preparation , biomaterial of nutrients transport
and transplantation is very complex process.
It is difficult to achieve cell diffrentiation into desired cell type and
ensuring their nutrient supply after implantation into the body.
There may be obstacles to growing cells in sufficient quantities.
The time necessary to develops cells in culture before they can be used
and possible lack of function at the donar site are some other
limitations.
Reference• Tannishtha Reya, Sean J. Morrison, Michael F. Clarke & Irving L. Weissman (2001). Stem cells, cancer,
and cancer stem cells. Nature. 414 . 105-111.
• Chad A. Cowan, Irina Klimanskaya, Jill McMahon, Jocelyn Atienza, Jeannine Witmyer, Jacob P. Zucker,
Shunping Wang, Cynthia C. Morton, Andrew P. McMahon, Doug Powers, and Douglas A. Melton.
(2004). Derivation of Embryonic Stem-Cell Lines from Human Blastocysts. The new england journal
Of medicine. 350: 13. 1353-1356.
• Paolo Bianco & Pamela Gehron Robey.(2001). Stem cells in tissue engineering. Nature, 414. 118-121.
• Krishnarao Appasani, Raghu K. Appasani : Stem Cells & Regenerative Medicine: From Molecular
Embryology to Tissue Engineering.19: 45: 103:195.
• Stock, U. A. & Vacanti, J. P. Tissue engineering: current state and prospects. Annu. Rev. Med. 52, 443–
451 (2001).
• Schneider MD. Regenerative medicine: Prometheus unbound. Nature 2004,432: 451-453.
• Langer R and Vacanti JP. Tissue engineering. Science 1993, 260: 920-926.
• Bianco, P., Riminucci, M., Gronthos, S. & Robey, P. G. (2001). Bone marrow stromal stem cells: nature,
biology, and potential applications. Stem Cells 19, 180–192.
• Langstaff, S. et al. (1999). Resorbable bioceramics based on stabilized calcium phosphates. Part I:
rational design, sample preparation and material characterization. Biomaterials 20, 1727–1741.
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