Tissue regeneration is presently
leaping ahead far faster than I expected.
The need is simply too real and the available volunteers too many. Suddenly they all have a choice and who wants
to do anything final when it is obvious that a better way will be available in
a few short months.
Thus, however inconvenient, tissue
removal will be now postponed as much as possible until therapies such as the ones
described herein become available.
The basic protocol will likely be
a case of removing cells from a pig organ to leave the collagen structure. Then the patients own cells are per fused
into the structure and once well established, the new organ is placed into the
patient.
In the first case they were able
to place a matrix to substitute for missing muscle mass with splendid results.
Tissue Regeneration with Extracellular Matrices and BioDome
Regenerative Sleeve
JUNE 23, 2011
Left- Biological scaffolds made of extracellular matrices, Center - mound of ECM powder or pixie dust that regenerate finger tips, Right - pixie dust in a test tube
Stephen Badylak is a leading researcher on tissue regeneration. Here is a link to his publications.
It appears that they are having success with inducing the regeneration of muscle tissue using extracellular matrices and bioscaffolds and using recellularized tissue. They hope to regenerate whole limbs with biodome regenerative sleeve which will control the conditions around a wound to allow for regeneration.
Badylak was featured in a 60 minutes feature in late 2009 on growing body parts.
Badylak is featured in the July/August 2011 Discover Magazine for his work in regenerating the muscle tissue in the leg of marine Corporal Isaias Hernandez.
Partial regeneration of leg muscle in Corporal Hernandez.
In the case of Corporal Hernandez, his arms and legs were injured when
a mortar exploded while he was hauling a television to a military vehicle in
preparation for an upcoming trip. 70% of the muscle in his right thigh was
destroyed by a mortar. His right leg received the worst of the shrapnel,
initially doctors advised him to have the leg amputated. Instead Corporal
Hernandez was put on a fitness regime to build up his existing muscle; surgeons
then cut open his thigh and inserted a thin slice of the extracellular matrix.
After a few weeks Corporal Hernandez found his leg rapidly growing in bulk and
strength.
Researchers at the McGowan Institute hope to eventually be able to restore not only muscle but complete limbs as well. While these types of animal hormone based therapies remain controversial, it’s difficult to argue against saving life and limb.
Limb Regeneration research with a biodome regenerative sleeve
Previous research on vertebrate limb regeneration indicates there are
several mediating factors involved during the re-growth process. These factors
are both biochemical and biophysical. While the phenomenon of adult limb
regeneration does not occur naturally in mammalian species, prior research has
focused mainly on biochemical modes of stimulating tissue growth and
regeneration. The BioDome was aimed at developing a new experimental tool to
permit the more systematic study of the impact of biophysical and biochemical
factors on mammalian tissue regeneration. The BioDome is a multi-component
sleeve assembly that encompasses the wound site of an amputated murine digit
and provides an environment conducive to tissue regeneration. The
studies showed that the BioDome was effective in supporting early stages of
murine digit tip regeneration when combined with a porcine urinary bladder
matrix (UBM) pepsin digest and electrical stimulation. The hydrated inner
environment of the BioDome influenced regeneration, with additional effects
seen with the application of electrical stimulation and pharmacological
treatments.
Residual dendrimer amine groups were modified with incorporate COOH
group containing biomolecules such as cell adhesion peptides into collagen
scaffolds. YIGSR, as a model cell adhesion peptide, was incorporated into both
the bulk structure of the gels and onto the gel surface. The effects of the
peptide modified collagen gels on corneal epithelial cell behavior were
examined with an aim of improving the potential of these materials as
tissue-engineering scaffolds. YIGSR was first chemically attached to dendrimers
and the YIGSR attached dendrimers were then used as collagen crosslinkers,
incorporating the peptide into the bulk structure of the collagen gels. YIGSR
was also attached to the surface of dendrimer crosslinked collagen gels through
reaction with excess amine groups. The YIGSR modified dendrimers were
characterized by H-NMR and MALDI mass spectra. The amount of YIGSR incorporated
into collagen gels was determined by (125)I radiolabelling at maximum to be
3.1-3.4 x 10(-2)mg/mg collagen when reacted with the bulk and 88.9-95.6
microg/cm(2) when attached to the surface. The amount of YIGSR could be tuned
by varying the amount of peptide reacted with the dendrimer or the amount of
modified dendrimer used in the crosslinking reaction. It was found that YIGSR
incorporation into the bulk and YIGSR modification of surface promoted the
adhesion and proliferation of human corneal epithelial cells as well as neurite
extension from dorsal root ganglia.
The therapy of choice for end-stage liver disease is whole-organ liver
transplantation, but this option is limited by a shortage of donor organs.
Cell-based therapies and hepatic tissue engineering have been considered as
alternatives to liver transplantation, but neither has proven effective to
date. A regenerative medicine approach for liver replacement has recently been
described that includes the use of a three-dimensional organ scaffold prepared
by decellularization of xenogeneic liver. The present study investigates a new,
minimally disruptive method for whole-organ liver decellularization and three
different cell reseeding strategies to engineer functional liver tissue.
Methods: A combination of enzymatic, detergent, and mechanical methods are
used to remove all cells from isolated rat livers. Whole-organ perfusion is used
in a customized organ chamber and the decellularized livers are examined by
morphologic, biochemical, and immunolabeling techniques for preservation of
the native matrix architecture and composition. Three different methods for
hepatocyte seeding of the resultant three-dimensional liver scaffolds are
evaluated to maximize cell survival and function: (1) direct parenchymal
injection, (2) multistep infusion, or (3) continuous perfusion. Results: The
decellularization process preserves the three-dimensional macrostructure, the
ultrastructure, the composition of the extracellular matrix components, the
native microvascular network of the liver, and the bile drainage system, and up
to 50% of growth factor content. The three-dimensional liver matrix reseeded with
the multistep infusion of hepatocytes generated ∼90% of cell engraftment and
supported liver-specific functional capacities of the engrafted cells,
including albumin production, urea metabolism, and cytochrome P450 induction.
Conclusions: Whole-organ liver decellularization is possible with
maintenance of structure and composition suitable to support functional
hepatocytes.
The definitive treatment for end stage organ failure is orthotropic
transplantation. However, the demand for transplantation far exceeds the number
of available donor organs. A promising tissue-engineering/regenerative-medicine
approach for functional organ replacement has emerged in recent years. Decellularization
of donor organs such as heart, liver, and lung can provide an acellular,
naturally occurring three dimensional biologic scaffold material that can then
be seeded with selected cell populations. Preliminary studies in animal
models have provided encouraging results for the proof of concept. However,
significant challenges for three dimensional organ engineering approach remain.
This manuscript describes the fundamental concepts of whole-organ engineering,
including characterization of the extracellular matrix as a scaffold, methods
for decellularization of vascular organs, potential cells to reseed such a
scaffold, techniques for the recellularization process and important aspects
regarding bioreactor design to support this approach. Critical challenges and
future directions are also discussed. Expected final online publication date
for the Annual Review of Biomedical Engineering Volume 13 is July 15, 2011.
Please see http://www.annualreviews.org/catalog/pubdates.aspx
for revised estimates.
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