Wharton’s Jelly Mesenchymal Stem Cells: Differentiation Capacity Showing its Role in Bone Tissue Engineering
Corresponding email: rizal@eng.ui.ac.id
Published at : 27 Nov 2020
Volume : IJtech
Vol 11, No 5 (2020)
DOI : https://doi.org/10.14716/ijtech.v11i5.4309
Rizal, R., Syaidah, R., Evelyn, E., Hafizh, A., Frederich, J., 2020. Wharton’s Jelly Mesenchymal Stem Cells: Differentiation Capacity Showing its Role in Bone Tissue Engineering. International Journal of Technology. Volume 11(5), pp. 1005-1014
| Rizal Rizal | Biomedical Engineering, Department of Electrical Engineering, Faculty of Engineering, Universitas Indonesia, Depok, West Java, 16424, Indonesia |
| Rahimi Syaidah | Department of Histology, Faculty of Medicine, Universitas Indonesia, Depok, West Java, 16424, Indonesia |
| Evelyn Evelyn | Undergraduate Program in Biomedical Engineering, Department of Electrical Engineering, Faculty of Engineering, Universitas Indonesia, Depok, West Java, 16424, Indonesia |
| Alif Hafizh | Undergraduate Program in Biomedical Engineering, Department of Electrical Engineering, Faculty of Engineering, Universitas Indonesia, Depok, West Java, 16424, Indonesia |
| Josh Frederich | Undergraduate Program in Biomedical Engineering, Department of Electrical Engineering, Faculty of Engineering, Universitas Indonesia, Depok, West Java, 16424, Indonesia |
Wharton’s jelly mesenchymal stem cells (WJ-MSCs) is
one of the best sources of mesenchymal stem cells (MSCs) that suggest both
embryonic and adult stem cell characteristics. Before being applied in clinical
application, the isolated MSCs should be tested to assess their quality,
including differentiation capacity, phenotype characterization, and
morphological appearance. This research aims to quantify the differentiation
capacity of WJ-MSCs isolated using explant method. The WJ-MSCs cells were grown
out from Wharton’s jelly tissue and the isolated cells adhered in T25 plastic
flask. The isolated cells expressed high amount of MSC surface marker which are
CD105 (99.97±0.06%), CD73 (99.97±0.06%), and CD90 (99.12±0.25%). The cells can
be differentiated into adipocytes, chondrocytes, and osteocytes. The
quantification showed that the amount of mineralization in osteoblastogenesis,
production of lipid droplet in adipogenic differentiation, and production of
glycosaminoglycan in chondrogenesis were noticeably higher in differentiated
cells than non-differentiated cells. In conclusion, the isolated cells fulfill
the minimum criteria of MSCs that can be used in research or clinical
application. The great differentiation capacity of the cells into osteocytes
and chondrocytes indicate that the cells are suitable in bone tissue
engineering application, both for research and clinical application.
Adipocytes; Chondrocytes; Differentiation capacity; Osteocytes; WJ-MSCs
Present materials, which are incorporated with osteoinductive properties, are continually developed for bone tissue engineering utilization to generate osteogenesis at the implant site. Graphene, which is generally a monoatomic two-dimensional sheet-like material with sp2-hybridized carbon atoms arranged in a hexagonal or honeycomb-like structure, and its thickness identical to an atom diameter, is one example of these materials with documented pro-osteogenic effects (Hermenean et al., 2016; Kusrini et al., 2019). However, it possesses a challenge to produce the materials (Supriadi et al., 2017). Another example is mesoporous silica nanoparticles (MSN). Osteogenic agents are added to the MSNs augment the bone regeneration process (Narayan et al., 2018). Porous materials are widely used as adsorbents, catalysts, and catalyst support due to their large surface area and pore volume characteristics (Wilson and Mahmud, 2015). However, to increase bone healing recovery, those materials should be combined with multipotent cells that have the properties of high self-proliferation and differentiation into bone-related cells.
Multipotent cells with high capacity of
self-proliferation that can be derived from almost all parts of the body,
including neonatal byproducts, bone marrow, adipose tissue, and dental tissue,
are called Mesenchymal stem cells (MSCs) (Hass et
al., 2011; Shivakumar et al., 2019). The MSCs hold a promising potential
application for regenerative disease and immunomodulation (Abdallah and Kassem, 2008). These have been
approved for the treatment of various diseases such as Crohn-related
enterocutaneous fistular disease and graft versus host disease (Galipeau and Sensébé, 2018). The MSCs have also
been explored to address several immunological disease (Ghannam
et al., 2010), bone and cartilage defects (Krampera
et al., 2006), neurological degeneration (Karussis
et al., 2010), and cardiovascular diseases (Ranganath
et al., 2012).
Several findings suggested that birth byproducts have better
proliferation and differentiation capacity (Anzalone et
al., 2010; Hass et al., 2011).
The MSCs can be isolated from various birth byproducts including amniotic
membrane and fluid (Wolbank et al., 2007; Utama, 2018), umbilical cord (Van Pham et
al., 2016),
Wharton’s jelly
tissue (Widowati et al., 2019), and umbilical cord
blood (Bieback and Netsch, 2016). Isolated MSCs from
neonatal-derived tissues also have both embryonic and adult stem cell characteristics
(Arutyunyan et al., 2016).
Wharton’s jelly tissues are part of the umbilical cord that are
considered as one of the finest sources of MSCs. The advantages of using these
tissues are ethical consideration, their availability, and non-invasive isolation
procedure (Hass et al., 2011). Before their clinical application, there are several quality controls
to examine the quality of WJ-MSCs. The minimal criteria that have been accepted
in both industrial and basic research application has been published by the
International Society for Cellular Therapy (ISCT) (Dominici et
al., 2006).
There are three
minimal criteria for MSCs: adherence to plastic, positive (>95%) for CD105,
CD73, and CD90, and can be differentiated into osteocytes, chondrocytes, and
adipocytes.
The aspects that may affect the differentiation capacity of MSCs are
tissue origin, isolation method, culture condition, and cells passage (Ahern
et al., 2011; Hass et al., 2011; Nepali et al., 2018; Rizal et al., 2019). They also can be trans-differentiated into
ectodermal lineage and endodermal lineage cells, including ?-pancreas (Ullah
et al., 2019), neuronal cells (Cortés-Medina
et al., 2019), and cardiomyocytes (Arslan
et al., 2018). This differentiation
capacity makes stem cells prospective for transplantation, thus having the
ability to repair many organ disfunctions. In addition, MSCs are able to
migrate and differentiate in the area of injury using the ability called homing
capacity (Lin et al., 2017; Ullah et al., 2020). These benefits make the research of exploring the
potential of MSCs very popular (Zakrzewski et al., 2019).
Differentiation capacity into osteocytes is one of the strengths of
WJ-MSCs that can be applied in bone tissue engineering (Ansari et
al., 2018).
The WJ-MSCs
reveal all characteristics of functional osteocytes/osteoblasts due to its
osteogenic gene expression, the ability to adhere in scaffold, and expression
of extracellular matrix mineralization (Todeschi
et al., 2015). They have been successfully transplanted into patients to treat
osteonecrosis and exhibited improvement in the joint function and also relieved
the pain (Cai et al., 2014).
Compared with bone marrow mesenchymal stem cells (BM-MSCs), the
application of WJ-MSCs in bone tissue engineering has several advantages. The
isolation procedure of WJ-MSCs are non-invasive because it comes from byproduct
waste pain (Wang et al., 2016). The WJ-MSCs also have low immunogenicity that enable us to use these
cells in both autologous and allogenic transplantation. When transplanted into
human body, WJ-MSCs are protected against lysis by NK cells because these cells
express low quantity of primary major histocompatibility class I (MHCI) and
class II (MHCII) proteins (Kalaszczynska and Ferdyn, 2015). There are no teratoma formation after
transplantation of WJ-MSCs in mice, as well as the patients (Ding,
2015).
Present study strives to quantify the differentiation capacity of MSCs
into three different mesodermal cells lineage: adipocytes, chondrocytes, and
osteocytes. Because of the heterogeneity of stem cells, the quantification of
the quality of stem cells become an important criterion in the quality check of
MSCs before being transplanted into human body, and in future all the minimal
criteria of stem cells should be measurable to ease the quality control check
of MSCs.
The current study indicates that the WJ-MSCs, isolated
through explant methods, generate high-quality stem cells that are in line with
mesenchymal stem cell criteria. The isolated WJ-MSCs can be differentiated into
adipocytes, chondrocytes, and adipocytes. This capacity can be quantified,
producing better determination on the quality of stem cells and their role in
bone tissue engineering.
This study was supported by a grant from
Universitas Indonesia, PUTI Prosiding 2020, contract no.
NKB-912/UN.RST/HKP.05.00/2020.
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