A Cross-Platform Challenge Behind the Role of Human Mesenchymal Stromal Cells in Organ Transplantation
Mini Review
Organ transplantation has become an essential treatment for saving
and prolonging lives in a wide range of clinical disorders. It is a
complex procedure and often convoluted by distinct issues related to
clinical outcome and number of donors [1]. Recent attempts to overcome
these problems have been demonstrated in the field of regenerative
medicine [2]. Regenerative medicine is a branch of medicine involved in
the development of methods for the regeneration and repair of tissues
and organs damaged by age, diseases or congenital defects. It
encompasses numerous strategies including the use of biomaterials, stem
cells and bio-cues or any combinations there of, to promote tissue
healing [3]. In this context, human bone marrow stromal stem cells
(MSC's) have proved to be an effective source for transplantation due to
their capacity to self- renew and differentiate both in in vitro and in vivo
while restraining concerns regarding immune response and ethical and
legal administration [4]. MSC can be isolated from a wide range of
foetal and adult tissues including bone marrow, placenta, umbilical
cord, dental pulp, tendons adipose and etc. However, MSC's are scarce
within tissues so that their use in clinical applications is strictly
limited [5]. To date, the shortage of these cells is addressed by
expanding MSC's by in vitro cell culture systems. Two dimensional
(2D) plastic cell cultures have been the preferred methods for decades
as relatively simple and highly reproducible.
After being isolated, cells are seeded on flat surfaces and easily
controlled, analysed and manipulated. However, 2D cultures induce MSC's
to lose their stemness and indeed their therapeutic potential in
restoring tissues and organs. Structurally, 2D cultures fail to resemble
the composition and structure of the native microenvironment or niche
onto which MSC’s reside [6]. The niche are specialised microenvironments
that regulate stem cell fate by providing essential cues in the form of
cells, ECM and soluble factors [7]. Recently, these niche-based
features have been recapitulated by 3D cultures which have conferred a
high degree of clinical and biological relevance to in vitro
models. Especially, those derived from MSC's offer the potential to
recapitulate some of the complex aspects of tissue development and
homeostasis while addressing fundamental questions about diseases and
their progress. In traditional 2D monolayer culture, MSC’s often
decrease their replicative ability and differentiation potentials as the
passage number increased.
In contrast, 3D cultures encourage MSC's to behave morphologically
and functionally different. 3D techniques built on fundamentals of
cell-cell and cell-matrix interactions whereby cells are often embedded
in matrices or scaffolds and encouraged to proliferate and polarise
according to the organ of origin. Collagen, chitosan, polycaprolactone
(PLC), polyethylene glycol (PEG) are some examples of biomaterials that
have greatly contributed to improve our understanding not only on MSC
biology, but also to aid in developing new therapies for a large number
of critical diseases.
However, the current 3D cultures still fail to resemble the complex
vascular systems that support tissues for oxygenation, nutrients, and
waste removal, leading multi-factorial disorders (e.g. diabetes) to be
unsuccessful studied and/or treated in vivo [8] . Progress in the
study of stem cell technology has enabled the development of
multicellular 3D cell cultures such as spheroids and organoids. Although
they differ in both features and functions, these techniques employ
standard tissue culture set up for the self-renewal and organisation of
cells into specific multicellular tissue proxies. Once encapsulated
within a biomaterial and/or in presence of suitable external cues, MSC’s
have shown capabilities to form anatomical structures made by clusters
of functionalised cells that displayed native phenotypic and
morphological signatures [9] . Within organoids, in particular, the
anti-inflammatory and angiogenesis properties as well as stemness and
differentiation of MSC's have been found to be extremely enhanced after
transplantation. Compared with spheroids, organoids are constructed from
adult or pluripotent stem cells and yield systems that reflect the
genomic makeup of a patient [10]. For instance, Ishida et al., by
creating conditions that resembling intestinal injury, reprogrammed
MSC's which in turn promoted the growth of colon organoids [11].
Moreover, combination of MSC's with epithelia and tooth germ led the
development of new teeth which displayed normal structures and
neuro-activities [12]. This is an obvious advantage as organoids provide
stable systems amenable to extended cultivation and manipulation of
MSC's while being more representative of in vivo physiology [13].
Given that, there are still key limitations that continue to conceal
their clinical translation including their reproducibility, scalability
and safety profile. It is believed that the introduction of more complex
structures including vascular and immune systems and the presence of a
defined microenvironment capable to regulate the spatiotemporal control
of cell activities could lead this endeavour soon a reality. Organoid
systems have already proven themselves to be a great tool for
regenerative medicine, and their recent combination with innovative
platforms such as nanomaterials has offered unmatched possibilities for
creating complex and functional organs that more faithfully recapitulate
the in vivo situation [14]. Therefore, the combined emergence of
these new technologies raise hopes for the development of novel methods
capable to meet the necessary MSC numbers required for organ
transplantation and the time and cost limitations associated to their in vitro manipulation.
Combination of Salinity and Sodicity Levels
Facilitates Screening of Medicinal Crop Linseed
(Linum Usitatissium) -https://biomedres01.blogspot.com/2020/01/combination-of-salinity-and-sodicity.html
More BJSTR Articles : https://biomedres01.blogspot.com
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.