• International Journal of Technology (IJTech)
  • Vol 11, No 5 (2020)

Wharton’s Jelly Mesenchymal Stem Cells: Differentiation Capacity Showing its Role in Bone Tissue Engineering

Wharton’s Jelly Mesenchymal Stem Cells: Differentiation Capacity Showing its Role in Bone Tissue Engineering

Title: Wharton’s Jelly Mesenchymal Stem Cells: Differentiation Capacity Showing its Role in Bone Tissue Engineering
Rizal Rizal, Rahimi Syaidah, Evelyn Evelyn, Alif Hafizh, Josh Frederich

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Cite this article as:
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
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Wharton’s Jelly Mesenchymal Stem Cells: Differentiation Capacity Showing its Role in Bone Tissue Engineering

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.


Supplementary Material
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Abdallah, B.M., Kassem, M., 2008. Human Mesenchymal Stem Cells: From Basic Biology to Clinical Applications. International Journal of Gene therapy, Volume 15(2), pp. 109–116

Ahern, B.J., Schaer, T.P., Terkhorn, S.P., Jackson, K.V., Mason, N.J., Hankenson, K.D., 2011. Evaluation of Equine Peripheral Blood Apheresis Product, Bone Marrow, and Adipose Tissue as Sources of Mesenchymal Stem Cells and their Differentiation Potential. American Journal of Veterinary Research, Volume 72(1), pp. 127–133

Ansari, A.S., Yazid, M.D., Sainik, N.Q.A.V., Razali, R.A., Saim, A.B., Idrus, R.B.H., 2018. Osteogenic Induction of Wharton’s Jelly-Derived Mesenchymal Stem Cell for Bone Regeneration: A Systematic Review. Stem Cells International, Volume 2018(4), pp. 117

Anzalone, R., Iacono, M.L., Corrao, S., Magno, F., Loria, T., Cappello, F., Zummo, G., Farina, F., Rocca, G.L., 2010. New Emerging Potentials for Human Wharton’s Jelly Mesenchymal Stem Cells: Immunological Features and Hepatocyte-like Differentiative Capacity. International Journal of Stem Cells and Development, Volume 19(4), pp. 423–438

Arslan, Y.E., Galata, Y.F., Arslan, T.S., Derkus, B., 2018. Trans-differentiation of Human Adipose-Derived Mesenchymal Stem Cells into Cardiomyocyte-like Cells on Decellularized Bovine Myocardial Extracellular Matrix-based Films. Journal of Materials Science: Materials in Medicine, Volume 29(127), https://doi.org/10.1007/s10856-018-6135-4

Arutyunyan, I., Elchaninov, A., Makarov, A., Fatkhudinov, T., 2016. Umbilical Cord as Prospective Source for Mesenchymal Stem Cell-based Therapy. Stem Cells International, Volume 2016(3), pp. 117

Baer, P.C., Geiger, H., 2012. Adipose-Derived Mesenchymal Stromal/Stem Cells: Tissue Localization, Characterization, and Heterogeneity. Stem Cells International, Volume 2012(3), pp. 111

Bieback, K., Netsch, P., 2016. Isolation, Culture, and Characterization of Human Umbilical Cord Blood-Derived Mesenchymal Stromal Cells. In Mesenchymal Stem Cells, pp. 245–258. Humana Press, New York

Cai, J., Wu, Z., Huang, L., Chen, J., Wu, C., Wang, S., Deng, Z., Wu, W., Luo, F., Tan, J., 2014. Cotransplantation of Bone Marrow Mononuclear Cells and Umbilical Cord Mesenchymal Stem Cells in Avascular Necrosis of the Femoral Head. In: Transplantation Proceedings, Volume 46(1), pp. 151–155

Cortés-Medina, L.V., Pasantes-Morales, H., Aguilera-Castrejon, A., Picones, A., Lara-Figueroa, C.O., Luis, E., Montesinos, J.J., Cortés-Morales, V.A., Ruiz, M.P.D.L.R.,  Hérnandez-Estévez, E., Bonifaz, L.C., Alvarez-Perez, M.A., Ramos-Mandujano, G., 2019. Neuronal Transdifferentiation Potential of Human Mesenchymal Stem Cells from Neonatal and Adult Sources by a Small Molecule Cocktail. Stem Cells International, Volume 2019, pp. 1–13

Dilogo, I.H., Primaputra, M.R.A., Pawitan, J.A., Liem, I.K., 2017. Modified Masquelet Technique using Allogeneic Umbilical Cord-Derived Mesenchymal Stem Cells for Infected Non-Union Femoral Shaft Fracture with a 12 cm Bone Defect: A Case Report. International Journal of Surgery Case Reports, Volume 34, pp. 1116

Ding, D.C., Chang, Y.H., Shyu, W.C., Lin, S.Z., 2015. Human Umbilical Cord Mesenchymal Stem Cells: A New Era for Stem Cell Therapy. Cell Transplantation, Volume 24(3), pp. 339347

Dominici, M.L.B.K., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F.C., Krause, D.S., Deans, R.J., Keating, A., Prockop, D.J., Horwitz, E.M., 2006. Minimal Criteria for Defining Multipotent Mesenchymal Stromal Cells. The International Society for Cellular Therapy Position Statement. International Journal of Cytotherapy, Volume 8(4), pp. 315–317

Galipeau, J., Sensébé, L., 2018. Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities. International Journal of Cell stem cell, Volume 22(6), pp. 824–833

Ghannam, S., Bouffi, C., Djouad, F., Jorgensen, C., Noël, D., 2010. Immunosuppression by Mesenchymal Stem Cells: Mechanisms and Clinical Applications. International Journal of Stem cell Research & Therapy, Volume 1(2), pp. 1–7

Hass, R., Kasper, C., Böhm, S., Jacobs, R., 2011. Different Populations and Sources of Human Mesenchymal Stem Cells (MSC): A Comparison of Adult and Neonatal Tissue-Derived MSC. International Journal of Cell Communication and Signaling, Volume 9(12), pp. 1–14

Hermenean, A., Dinescu, S., Ionita, M., Costache, M., 2016. The Impact of Graphene Oxide on Bone Regeneration Therapies. IntechOpen, pp. 151–167

Kalaszczynska, I., Ferdyn, K., 2015. Wharton’s Jelly Derived Mesenchymal Stem Cells: Future of Regenerative Medicine? Recent Findings and Clinical Significance. BioMed Research International, Volume 2015(3), pp. 111

Karussis, D., Karageorgiou, C., Vaknin-Dembinsky, A., Gowda-Kurkalli, B., Gomori, J.M., Kassis, I., Bulte, J.W.M., Petrou, P., Ben-Hur, T., Slavin, S., 2010. Safety and Immunological Effects of Mesenchymal Stem Cell Transplantation in Patients with Multiple Sclerosis and Amyotrophic Lateral Sclerosis. International Journal of Archives of Neurology, Volume 67(10), pp. 1187–1194

Kim, N., Cho, S.G., 2013. Clinical Applications of Mesenchymal Stem Cells. The Korean Journal of Internal Medicine, Volume 28(4), pp. 387–402

Kosinski, M., Figiel-Dabrowska, A., Lech, W., Wieprzowski, L., Strzalkowski, R., Strzemecki, D., Cheda, L., Lenart, J., Domanska-Janik, K., Sarnowska, A., 2020. Bone Defect Repair using a Bone Substitute Supported by Mesenchymal Stem Cells Derived from the Umbilical Cord. Stem Cells International, Volume 2020, pp. 1–15

Krampera, M., Pizzolo, G., Aprili, G., Franchini, M., 2006. Mesenchymal Stem Cells for Bone, Cartilage, Tendon and Skeletal Muscle Repair. International Journal of Bone, Volume 39(4), pp. 678–683

Kusrini, E., Suhrowati, A., Usman, A., Degirmenci, D.V., Khalil, M., 2019. Synthesis and Characterization of Graphite Oxide, Graphene Oxide and Reduced Graphene Oxide from Graphite Waste using Modified Hummers’s Method and Zinc as Reducing Agent. International Journal of Technology, Volume 10(6), pp. 1093–1104

Kyurkchiev, D., Bochev, I., Ivanova-Todorova, E., Mourdjeva, M., Oreshkova, T., Belemezova, K., Kyurkchiev, S., 2014. Secretion of Immunoregulatory Cytokines by Mesenchymal Stem Cells. World Journal of Stem Cells, Volume 6(5), pp. 552–570

La Rocca, G., Lo Iacono, M., Corsello, T., Corrao, S., Farina, F., Anzalone, R., 2013. Human Wharton's Jelly Mesenchymal Stem Cells Maintain the Expression of Key Immunomodulatory Molecules when Subjected to Osteogenic, Adipogenic and Chondrogenic Differentiation in vitro: New Perspectives for Cellular Therapy. Current Stem Cell Research & Therapy, Volume 8(1), pp. 100113

Lin, W., Xu, L., Zwingenberger, S., Gibon, E., Goodman, S.B., Li, G., 2017. Mesenchymal Stem Cells Homing to Improve Bone Healing. Journal of Orthopaedic Translation, Volume 9, pp. 19–27

Moraes, D.A., Sibov, T.T., Pavon, L.F., Alvim, P.Q., Bonadio, R.S., Da Silva, J.R., Pic-Taylor, A., Toledo, O.A., Marti, L.C., Azevedo, R.B., Oliveira, D.M., 2016. A Reduction in CD90 (THY-1) Expression Results in Increased Differentiation of Mesenchymal Stromal Cells. Stem Cell Research & Therapy, Volume 7(1), pp. 1–14

Narayan, R., Nayak, U.Y., Raichur, A.M., Garg, S., 2018. Mesoporous Silica Nanoparticles: A Comprehensive Review on Synthesis and Recent Advances. Pharmaceutics, Volume 10(3), pp. 1–49

Nepali, S., Park, M., Lew, H., Kim, O., 2018. Comparative Analysis of Human Adipose-Derived Mesenchymal Stem Cells from Orbital and Abdominal Fat. Stem Cells International, Volume 2018(3), pp. 19

Obtulowicz, P., Lech, W., Strojek, L., Sarnowska, A., Domanska-Janik, K., 2016. Induction of Endothelial Phenotype from Wharton's Jelly-Derived MSCs and Comparison of their Vasoprotective and Neuroprotective Potential with Primary WJ-MSCs in CA1 Hippocampal Region ex vivo. Cell Transplantation, Volume 25(4), pp. 715–727

Pierelli, L., Bonanno, G., Rutella, S., Marone, M., Scambia, G., Leone, G., 2001. CD105 (Endoglin) Expression on Hematopoietic Stem/Progenitor Cells. Leukemia & Lymphoma, Volume 42(6), pp. 1195–1206

Ranganath, S.H., Levy, O., Inamdar, M.S., Karp, J.M., 2012. Harnessing the Mesenchymal Stem Cell Secretome for the Treatment of Cardiovascular Disease. International Journal of Cell Stem Cell, Volume 10(3), pp. 244–258

Rizal, R., Kerans, F.F., Hermantara, R., Herningtyas, E.H., 2018. Isolation, Characterization, Proliferation, Differentiation, and Freeze-Thaw Survival of Human Wharton's Jelly Mesenchymal Stem Cells from Early and Late Passages. Bioscience Research, Volume 15(1), pp. 392–401

Rizal, R., Widodo, W.S., Wibowo, S., Munshy, U.Z., 2019. Effect of Serial Passage on Growth Kinetics, Biological Properties, and Differentiation into Adipocytes of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells. Majalah Kedokteran Bandung, Volume 51(3), pp. 127–133

Shivakumar, S.B., Lee, H.J., Son, Y.B., Bharti, D., Ock, S.A., Lee, S.L., Kang, Y.H., Park, B.W., Rho, G.J., 2019. In vitro Differentiation of Single Donor Derived Human Dental Mesenchymal Stem Cells into Pancreatic ? Cell-like Cells. International Journal of Bioscience reports, Volume 39(5), pp. 1–14

Supriadi, C.P., Kartini, E., Honggowiranto, W., Basuki, K.T., 2017. Synthesis and Characterization of Carbon Material Obtained from Coconut Coir Dust by Hydrothermal and Pyrolytic Processes. International Journal of Technology, Volume 8(8), pp. 1470–1478

Todeschi, M.R., ElBackly, R., Capelli, C., Daga, A., Patrone, E., Introna, M., Cancedda, R., Mastrogiacomo, M., 2015. Transplanted Umbilical Cord Mesenchymal Stem Cells Modify the in Vivo Microenvironment Enhancing Angiogenesis and Leading to Bone Regeneration. International Journal of Stem Cells and Development, Volume 24(13), pp. 1570–1581

Ullah, I., Lee, R., Oh, K.B., Hwang, S., Kim, Y., Hur, T.Y., Ock, S.A., 2020. Transdifferentiation of ?-1, 3-Galactosyltransferase Knockout Pig Bone Marrow Derived Mesenchymal Stem Cells into Pancreatic ?-like Cells by Microenvironment Modulation. Asian-Australasian Journal of Animal Sciences, Volume 33(11), pp. 1837–1847

Ullah, M., Liu, D.D., Thakor, A.S., 2019. Mesenchymal Stromal Cell Homing: Mechanisms and Strategies for Improvement. International Journal of Iscience, Volume 15, pp. 421–438

Utama, B.I., 2018. Isolation of Amniotic Fluid Mesenchymal Stem Cells (Af-Mscs) Obtained from Caesarean Sections. Andalas Obstetrics and Gynecology Journal, Volume 2(1), pp. 1–9

Van Pham, P., Truong, N.C., Le, P.T.B., Tran, T.D.X., Vu, N.B., Bui, K.H.T., Phan, N.K., 2016. Isolation and Proliferation of Umbilical Cord Tissue Derived Mesenchymal Stem Cells for Clinical Applications. International Journal of Cell and Tissue Banking, Volume 17(2), pp. 289–302

Wagner, W., Feldmann Jr, R.E., Seckinger, A., Maurer, M.H., Wein, F., Blake, J., Krause, U., Kalenka, A., Burgers, H., Saffrich, R., Wuchter, P., 2006. The Heterogeneity of Human Mesenchymal Stem Cell Preparations—Evidence from Simultaneous Analysis of Proteomes and Transcriptomes. Experimental hematology, Volume 34(4), pp. 536–548

Wagner, W., Horn, P., Castoldi, M., Diehlmann, A., Bork, S., Saffrich, R., Benes, V., Blake, J., Pfister, S., Eckstein, V., Ho, A.D., 2008. Replicative Senescence of Mesenchymal Stem Cells: A Continuous and Organized Process. PloS one, Volume 3(5), pp. 1–12

Wang, Q., Yang, Q., Wang, Z., Tong, H., Ma, L., Zhang, Y., Shan, F., Meng, Y., Yuan, Z., 2016. Comparative Analysis of Human Mesenchymal Stem Cells from Fetal-Bone Marrow, Adipose Tissue, and Warton's Jelly as Sources of Cell Immunomodulatory Therapy. International Journal of Human Vaccines & Immunotherapeutics, Volume 12(1), pp. 85–96

Widowati, W., Gunanegara, R.F., Rizal, R., Widodo, W.S., Amalia, A., Wibowo, S.H.B., Handono, K., Marlina, M., Lister, I.N.E., Chiuman, L., 2019. Comparative Analysis of Wharton’s Jelly Mesenchymal Stem Cell (WJ-MSCs) Isolated using Explant and Enzymatic Methods. In: Journal of Physics: Conference Series (Volume 1374, No. 1, p. 012024). IOP Publishing

Wilson, L.D., Mahmud, S.T., 2015. The Adsorption Properties of Surface-Modified Mesoporous Silica Materials with ß-Cylodextrin. International Journal of Technology, Volume 6(4), pp. 533–545

Wolbank, S., Peterbauer, A., Fahrner, M., Hennerbichler, S., Van Griensven, M., Stadler, G., Redl, H., Gabriel, C., 2007. Dose-Dependent Immunomodulatory Effect of Human Stem Cells from Amniotic Membrane: A Comparison with Human Mesenchymal Stem Cells from Adipose Tissue. International Journal of Tissue engineering, Volume 13(6), pp. 1173–1183

Zajdel, A., Ka?ucka, M., Kokoszka-Miko?aj, E., Wilczok, A., 2017. Osteogenic Differentiation of Human Mesenchymal Stem Cells from Adipose Tissue and Wharton’s Jelly of the Umbilical Cord. Acta Biochimica Polonica, Volume 64(2), pp. 365–369

Zakrzewski, W., Dobrzy?ski, M., Szymonowicz, M., Rybak, Z., 2019. Stem Cells: Past, Present, and Future. International Journal of Stem Cell Research & Therapy, Volume 10(68), pp. 1–22

Zhang, B., 2010. CD73: A Novel Target for Cancer Immunotherapy. Cancer Research, Volume 70(16), pp. 6407–6411