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General Medicine: Open Access
Editorial
Vishwakarma et al., General Med 2015, 3:2
http://dx.doi.org/10.4172/2327-5146.1000e108
Open Access
Neo-Bioartificial Whole Functional Organ Development Using Decellularization
and Stem Cells Repopulation Technology: Cutting Edge Strategy for Humanized
Organ Development
Vishwakarma SK, Bardia A and Khan AA*
Central Laboratory for Stem Cell Research & Translational Medicine, CLRD, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, Telangana, India
*Corresponding author: Khan AA, Central Laboratory for Stem Cell Research & Translational Medicine, CLRD, Deccan College of Medical Sciences, Kanchanbagh,
Hyderabad-500 058, Telangana, India, Tel: 91 40 24342954; Fax: +91 40 24342954; E-mail: [email protected]
Rec date: March 02, 2015 Acc date: March 04, 2015 Pub date: March 06, 2015
Copyright: © 2015 Vishwakarma SK et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Editorial
Shortage of available organs for organ transplantation in end stage
organ failure is a major challenge. Annually >10,00,000 patients die for
the want of the functional organ. Demand of donating organ for the
treatment of end stages organ failure has increased tremendously in
recent years. The knowledge of stem cells has proved its potential for
the treatment of various fatal diseases. Stem cells are known to
regenerate injured tissues or to replace the lost cells in a very effective
manner. Whole organ development requires not only the stem cells but
also the contiguous stem cell niche or microenvironment and
extracellular matrix with complete vasculature and integrity. Adding
up to the cell replacement therapy stem cells-based organ regeneration
has been successfully accomplished in clinics for organ failure of the
liver or kidney. Generation of biological or semi-biological organs
using stem cells could be an alternative approach to solve the shortage
of donor organs. Particularly, researchers have been looking for ways
to establish a whole organ using stem cells. Stem cells from various
sources have been tried to regenerate the damages organ system still
which stem cell type is used, it remains a challenge to reliably generate
large quantities of well-differentiated cells.
The recent breakthroughs and one specific trial in particular,
provide much closer evidence for clinical practice. Recently, the first
human tissue-engineered organ using stem cells was created and
transplanted successfully into a patient. In the first reported instance of
using stem cells to bioengineer a functional humanized organ, Paolo
Macchiarini and his colleagues used a patient’s own stem cells to
generate bronchus, and successfully grafted it into the patient to
replace her damaged bronchus. Macchiarini’s group bypassed the
problem of immune rejection by using allogenic stem cells [1,2]. Other
tissue regeneration efforts using stem cells have also been recently
made lots of breakthroughs, emphasizing the possiblities of using stem
cells in future tissue/organ transplants.
In recent year’s decellularization and recellularization approach for
whole organ construction has been emerged as exceptionally
promising technology [3]. Few landmark studies on complex organs
development, such as liver, heart, kidney and lung have provided a
better insight into the supremacy of the methodology. Encouraging
results from animal model studies have emerged a potential hope to
get the whole personalized functional organ for the end stage organ
failure patients. These bio-artificial organs provide micro vascular
structure for efficient supply of nutrient and oxygen to each and every
cell and solve the problem of availability of 3D-natural architecture
and organ scaffold, immune rejection and others.
General Med
ISSN:2327-5146 GMO
Seeding of specific type of cells with high proliferation and
controlled differentiation potential is necessary to repopulate the
decellularized organ scaffold (a process called repopulation/
recellularization). Although, a variety of organs have been used for
decellularization and recellularization to generate the functional organ.
None of them have proved their absolute potential to replace the
damaged organ/tissue. Liver becomes a more convenient organ in
terms of repopulation of decellularized organ because the major
population of cells is of parenchymal. Functionally this organ performs
more towards the detoxification and synthetic function. Hence, the
desired cells can be used as per the requirement of the organ. As in the
acute liver failure short-term support is needed to the failing liver. This
concept becomes more viable as extra-corporeal organ support using
xenogenic liver scaffolds repopulated with human hepatic stem cells
[4,5]. Still there are certain complications and issues which need to be
considered and solved before its clinical applications such as type of
organ scaffold, sterilization of the scaffold, integrity of the vasculature
and natural architecture within the scaffold, assessment of
immunological barriers, type of cells/tissue to regenerate functional
aspects of the regenerated organ, type of cells for infusion, route of cell
delivery, required induction factors and assessment of long-term cell
survival and engraftment.
Further studies are needed to determine the role of biological,
structural and mechanical factors responsible for the generation of
natural ECM with functional recovery. Petersen et al., and Ott et al. for
the first time demonstrated transplant survival for few hours of
repopulated lung scaffold into rats with adequate oxygen and CO2
exchange and appropriate pressure/volume relationships [6,7].
However the rat was died because of pulmonary oedema and/or
haemorrhage resulting in respiratory failure. This approach provided a
clue for the development of new organ by recellularization of
decellularized organ scaffolds. Following to the above study Song et al.,
generated a bioartificial rat kidney by decellularization and
recellularization approach using human umbilical cord blood derived
endothelial cells and showed urine production along with slight
macromolecular sieving and reabsorption potential.
Very recently our group has demonstrated the development of bioartificial organ from goat using decellularization technology [4,5-9].
This model provides more appropriate xenogenic source to plug the
gap between the shortages of available donor organs due to the
similarity in organ size and complexity and most importantly it has
very low risk of zoonosis. This model represents most accepted choice
for better understanding of whole organ regeneration and shows
promise for a suitable organ donor for the recipients waiting for organ
transplantation.
Volume 3 • Issue 2 • e108
Citation:
Vishwakarma SK, Bardia A, Khan AA (2015) Neo-Bioartificial Whole Functional Organ Development Using Decellularization and Stem
Cells Repopulation Technology: Cutting Edge Strategy for Humanized Organ Development. General Med 3: 1000e108. doi:
10.4172/2327-5146.1000e108
Page 2 of 2
In summary, the concept of decellularization and recellularization
has provided a new dimension for the development of bioartificial
organs which can find its clinical applications after further
advancements (Figure 1). However, development of bioartificial
functional organs based on the decellularization and recellularization
technology still remains challenging. Further vital research is needed
for the prediction of functional outcome ex vivo and in vivo such as
long-term survival, engraftment and cost effectiveness.
References
1. Macchiarini P, Jungebluth P, Go T, Asnaghi MA, Rees LE, et al. (2008)
2.
3.
4.
5.
6.
7.
8.
Figure 1: Schematic representation for the development of
functional humanized organ
General Med
ISSN:2327-5146 GMO
9.
Clinical transplantation of a tissue-engineered airway. The Lancent 372:
2023-2030.
Hollander A, Macchiarini P, Gordijn B, Birchall M (2009) The first stem
cell-based tissue-engineered organ replacement: implications for
regenerative medicine and society. Regen. Med 4: 147-148.
Badylak SF, Taylor D, Uygun K (2011) Whole-organ tissue engineering:
decellularization and recellularization of three-dimensional matrix
scaffolds. Annu Rev Biomed Eng 13: 27–53.
Khan AA, Vishwakarma SK, Bhavani PG, Hussain SW, Habeeb MA (2014)
Decellularized liver scaffold as a potential resource for the development of
functional humanized liver. Cytotherapy 16: S89.
Habeeb MA, Vishwakarma SK, Bhavani PG, Bardia A, Khan AA (2014)
Development of extra-corporeal bioartificial liver by repopulating the
decellularized goat liver scaffold using human hepatic progenitors. Journal
of Hepatology 60: S2-07.
Petersen TH, Calle EA, Zhao L, Lee EJ, Gui L (2010) Tissue-engineered
lungs for in vivo implantation. Science 329: 538–541.
Ott HC, Clippinger B, Conrad C, Schuetz C, Pomerantseva I, et al. (2010)
Regeneration and orthotopic transplantation of a bioartificial lung. Nature
Medicine 16: 927–933.
Vishwakarma SK, Bhavani PG, Bardia A, Abkari A, Murthy (2014)
Preparation of natural three-dimensional goat kidney scaffold for the
development of bioartificial organ. Indian Journal of Nephrology.
Rout S, Vishwakarma SK, Khan AA (2014) Decellularized Heart: A Step
towards Creating Personalized Bioengineered Organ. Current Science.
Volume 3 • Issue 2 • e108