Published date: Oct 31 2024

Journal Title: Gulf Education and Social Policy Review

Issue title: Gulf Education and Social Policy Review (GESPR): Volume 5, Issue 2

Pages: 158–174

DOI: 10.18502/gespr.v5i2.16916

Joaquín Villarreal BarragánDepartment of Biomedical Engineering and Biotechnology, Khalifa University, Abu Dhabi, United Arab Emirates

Mira MousaCenter of Biotechnology, Khalifa University, Abu Dhabi, United Arab Emirates

Nupur Kohlinupur.kohli@ku.ac.aeDepartment of Biomedical Engineering and Biotechnology, Khalifa University, Abu Dhabi, United Arab Emirates

In the UAE, current hospital policies mandate the disposal of biological waste, such as umbilical cords. However, this tissue represents a valuable source of therapeutic material like mesenchymal stem cells (MSCs) and their secretome. The disposal of this valuable therapeutic material imposes a significant burden on public health. In the United States alone, approximately 18,000 people per year are diagnosed with diseases that could be ameliorated with stem cell therapy. These individuals often remain untreated due to the lack of available stem cells, as current methods for MSC obtention, such as Bone Marrow-MSCs, require an invasive bone marrow aspirate procedure, which is painful and can pose risks to donors, including infection and prolonged recovery times. This paper advocates for policy reform to facilitate the collection, storage, and utilization of umbilical cords. By addressing regulatory barriers and implementing standardized protocols, hospitals in the UAE can not only contribute to advancements in regenerative medicine but also solidify the nation’s position as a leader in this emerging field, ultimately improving patient outcomes and reducing the disease burden both locally and regionally. This is particularly relevant given the significant burden of cardiovascular diseases and type 2 diabetes mellitus (T2DM) in the UAE, where 17.3% of the population aged 20 to 79 is affected with T2DM. Cardiovascular diseases and T2DM are few of the many disorders that can benefit from MSC therapy. Utilizing umbilical cord biowaste for such diseases can further build the UAE’s status as a hub for medical tourism and accentuate it’s growing prominence in the field of regenerative medicine.

Keywords: Regenerative therapy, Mesenchymal stem cells (MSCs), Umbilical cord, Biomedical waste

[1] Abbaspanah, B., Reyhani, S., & Mousavi, S. H. (2021). Applications of umbilical cord derived mesenchymal stem cells in autoimmune and immunological disorders: From literature to clinical practice. Current Stem Cell Research & Therapy, 16(4), 454–464. https://doi.org/10.2174/1574888X16999201124153000

[2] Alhawarat, F. M., Hammad, H. M., Hijjawi, M. S., Sharab, A. S., Abuarqoub, D. A., Al Shhab, M. A., & Zihlif, M. A. (2019). The effect of cycling hypoxia on MCF-7 cancer stem cells and the impact of their microenvironment on angiogenesis using human umbilical vein endothelial cells (HUVECs) as a model. PeerJ, 7, e5990. https://doi.org/10.7717/peerj.5990

[3] Atala, A., Cetrulo, K. J., Taghizadeh, R. R., Cetrulo, C. L., & Murphy, S. (Eds.). (2018). Perinatal stem cells: Research and theraphy (1st ed.). Academic Press.

[4] Azari, Z., Nazarnezhad, S., Webster, T. J., Hoseini, S. J., Brouki Milan, P., Baino, F., & Kargozar, S. (2022). Stem cell-mediated angiogenesis in skin tissue engineering and wound healing. Wound Repair and Regeneration, 30(4), 421–435. https://doi.org/10.1111/wrr.13033

[5] Beltrame, L. (2019). ‘It’s a family affair’: The discursive entanglement of social formations in public and private cord blood banking in Italy. Public Understanding of Science (Bristol, England), 28(8), 917–931. https://doi.org/10.1177/0963662519864017

[6] Bolli, R., Hare, J. M., Henry, T. D., Lenneman, C. G., March, K. L., Miller, K., Pepine, C. J., Perin, E. C., Traverse, J. H., Willerson, J. T., Yang, P. C., Gee, A. P., Lima, J. A., Moyé, L., Vojvodic, R. W., Sayre, S. L., Bettencourt, J., Cohen, M., Ebert, R. F., Simari, R. D., & the Cardiovascular Cell Therapy Research Network (CCTRN). (2018). Rationale and design of the SENECA (StEm cell iNjECtion in cAncer survivors) trial. American Heart Journal, 201, 54–62. https://doi.org/10.1016/j.ahj.2018.02.009

[7] Cao, Y., Gong, Y., Liu, L., Zhou, Y., Fang, X., Zhang, C., Li, Y., & Li, J. (2017). The use of human umbilical vein endothelial cells (HUVECs) as an in vitro model to assess the toxicity of nanoparticles to endothelium: A review. Journal of Applied Toxicology, 37(12), 1359–1369. https://doi.org/10.1002/jat.3470

[8] Danova-Alt, R., Heider, A., Egger, D., Cross, M., & Alt, R. (2012). Very small embryonic-like stem cells purified from umbilical cord blood lack stem cell characteristics. PLoS One, 7(4), e34899. https://doi.org/10.1371/journal.pone.0034899

[9] De La Torre, P., Jesús Pérez-Lorenzo, M., & Flores, I. A. (2019). Human placenta-derived mesenchymal stromal cells: A review from basic research to clinical applications. In M. T. Valarmathi (Ed.), Stromal cells—Structure, function, and therapeutic implications. IntechOpen. https://doi.org/10.5772/intechopen.76718

[10] Di Tomo, P., Alessio, N., Falone, S., Pietrangelo, L., Lanuti, P., Cordone, V., Santini, S. J., Di Pietrantonio, N., Marchisio, M., Protasi, F., Di Pietro, N., Formoso, G., Amicarelli, F., Galderisi, U., & Pandolfi, A. (2021). Endothelial cells from umbilical cord of women affected by gestational diabetes: A suitable in vitro model to study mechanisms of early vascular senescence in diabetes. The FASEB Journal, 35(6), e21662. Advance online publication. https://doi.org/10.1096/fj.202002072RR

[11] Dubai Health Authority DHA. (2021). Waste and Environmental Management. Health Regulation Sector. https://services.dha.gov.ae/sheryan/wps/portal/home/circular-details?circularRefNo= CIR-2021-00000256&fromHome=true

[12] Eapen, M., Rubinstein, P., Zhang, M.-J., Stevens, C., Kurtzberg, J., Scaradavou, A., Loberiza, F. R., Champlin, R. E., Klein, J. P., Horowitz, M. M., & Wagner, J. E. (2007). Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: A comparison study. Lancet, 369(9577), 1947–1954. https://doi.org/10.1016/S0140-6736(07)60915-5

[13] Fan, Y., Herr, F., Vernochet, A., Mennesson, B., Oberlin, E., & Durrbach, A. (2019). Human fetal liver mesenchymal stem cell-derived exosomes impair natural killer cell function. Stem Cells and Development, 28(1), 44–55. https://doi.org/10.1089/scd.2018.0015

[14] Farkhad, N. K., Mahmoudi, A., & Mahdipour, E. (2021). How similar are human mesenchymal stem cells derived from different origins? A review of comparative studies. Current Stem Cell Research & Therapy, 16(8), 980–993. https://doi.org/10.2174/1574888X16666210302151823

[15] Galderisi, U., Peluso, G., & Di Bernardo, G. (2022). Clinical trials based on mesenchymal stromal cells are exponentially increasing: Where are we in recent years? Stem Cell Reviews and Reports, 18(1), 23–36. https://doi.org/10.1007/s12015-021-10231-w

[16] García-Sánchez, D., Fernández, D., Rodríguez-Rey, J. C., & Pérez-Campo, F. M. (2019). Enhancing survival, engraftment, and osteogenic potential of mesenchymal stem cells. World Journal of Stem Cells, 11(10), 748–763. https://doi.org/10.4252/wjsc.v11.i10.748

[17] Han, Y., Yang, J., Fang, J., Zhou, Y., Candi, E., Wang, J., Hua, D., Shao, C., & Shi, Y. (2022). The secretion profile of mesenchymal stem cells and potential applications in treating human diseases. Signal Transduction and Targeted Therapy, 7(1), 92. https://doi.org/10.1038/s41392-022-00932-0

[18] Hauser, S., Jung, F., & Pietzsch, J. (2017). Human endothelial cell models in biomaterial research. Trends in Biotechnology, 35(3), 265–277. https://doi.org/10.1016/j.tibtech.2016.09.007

[19] Hoseini, S. M., Hosseini, E. S., Abessi, P., & Montazeri, F. (2024). Paracrine secretions and immunological activities of human mesenchymal stem cells: The key regenerative factors of microenvironment. Stem Cell Research & Therapy, 14(1), 1000636. https://doi.org/10.35248/2157-7633.24.14.636

[20] Hostettler, K. E., Gazdhar, A., Khan, P., Savic, S., Tamo, L., Lardinois, D., Roth, M., Tamm, M., & Geiser, T. (2017). Multipotent mesenchymal stem cells in lung fibrosis. PLoS One, 12(8), e0181946. https://doi.org/10.1371/journal.pone.0181946

[21] Hu, J., Yu, X., Wang, Z., Wang, F., Wang, L., Gao, H., Chen, Y., Zhao, W., Jia, Z., Yan, S., & Wang, Y. (2013). Long term effects of the implantation of Wharton’s jelly-derived mesenchymal stem cells from the umbilical cord for newly-onset type 1 diabetes mellitus. Endocrine Journal, 60(3), 347–357. https://doi.org/10.1507/endocrj.EJ12-0343

[22] Javan, M. R., Khosrojerdi, A., & Moazzeni, S. M. (2019). New insights into implementation of mesenchymal stem cells in cancer therapy: Prospects for anti-angiogenesis treatment. Frontiers in Oncology, 9, 840. https://doi.org/10.3389/fonc.2019.00840

[23] Jia, X., Xu, J., Gu, Y., Gu, X., Li, W., & Wang, Y. (2017). Vitamin D suppresses oxidative stressinduced microparticle release by human umbilical vein endothelial cells. Biology of Reproduction, 96(1), 199–210. https://doi.org/10.1093/biolre/bio142604

[24] Jiménez-Rosado, M., Perez-Puyana, V., & Romero, A. (2023). The use of biowaste for the production of biodegradable superabsorbent materials. Current Opinion in Food Science, 49, 100975. https://doi.org/10.1016/j.cofs.2022.100975

[25] Jovic, D., Yu, Y., Wang, D., Wang, K., Li, H., Xu, F., Liu, C., Liu, J., & Luo, Y. (2022). A brief overview of global trends in MSC-based cell therapy. Stem Cell Reviews and Reports, 18(5), 1525–1545. https://doi.org/10.1007/s12015-022-10369-1

[26] Kapinos, K. A., Briscombe, B., Gračner, T., Strong, A., Whaley, C., Hoch, E., Hlávka, J. P., Case, S. R., & Chen, P. G. (2017). Challenges to the sustainability of the U.S. public cord blood system. Rand Health. https://www.rand.org/content/dam/rand/pubs/research_reports/RR1800/RR1898/RAND_RR1898.pdf

[27] Kawashima, N., Noda, S., Yamamoto, M., & Okiji, T. (2017). Properties of dental pulp-derived mesenchymal stem cells and the effects of culture conditions. Journal of Endodontics, 43(9S), S31–S34. https://doi.org/10.1016/j.joen.2017.06.004

[28] Kocherova, I., Bryja, A., Mozdziak, P., Angelova Volponi, A., Dyszkiewicz-Konwińska, M., Piotrowska- Kempisty, H., Antosik, P., Bukowska, D., Bruska, M., Iżycki, D., Zabel, M., Nowicki, M., & Kempisty, B. (2019). Human umbilical vein endothelial cells (HUVECs) co-culture with osteogenic cells: From molecular communication to engineering prevascularised bone grafts. Journal of Clinical Medicine, 8(10), 1602. https://doi.org/10.3390/jcm8101602

[29] L., P. K., Kandoi, S., Misra, R., S., V., K., R., & Verma, R. S. (2019). The mesenchymal stem cell secretome: A new paradigm towards cell-free therapeutic mode in regenerative medicine. Cytokine & Growth Factor Reviews, 46, 1–9. https://doi.org/10.1016/j.cytogfr.2019.04.002

[30] Lee, W.-S., Kim, H. J., Kim, K.-I., Kim, G. B., & Jin, W. (2019). Intra-articular injection of autologous adipose tissue-derived mesenchymal stem cells for the treatment of knee osteoarthritis: A phase IIb, randomized, placebo-controlled clinical trial. Stem Cells Translational Medicine, 8(6), 504–511. https://doi.org/10.1002/sctm.18-0122

[31] Leng, Z., Sun, D., Huang, Z., Tadmori, I., Chiang, N., Kethidi, N., Sabra, A., Kushida, Y., Fu, Y.-S., Dezawa, M., He, X., & Young, W. (2019). Quantitative analysis of SSEA3+ cells from human umbilical cord after magnetic sorting. Cell Transplantation, 28(7), 907–923. https://doi.org/10.1177/0963689719844260

[32] Liau, L. L., Ruszymah, B. H. I., Ng, M. H., & Law, J. X. (2020). Characteristics and clinical applications of Wharton’s jelly-derived mesenchymal stromal cells. Current Research in Translational Medicine, 68(1), 5–16. https://doi.org/10.1016/j.retram.2019.09.001

[33] Liu, Y., Wang, L., Ai, J., & Li, K. (2024). Mitochondria in mesenchymal stem cells: Key to fate determination and therapeutic potential. Stem Cell Reviews and Reports, 20(3), 617–636. https://doi.org/10.1007/s12015-024-10681-y

[34] Maacha, S., Sidahmed, H., Jacob, S., Gentilcore, G., Calzone, R., Grivel, J.-C., & Cugno, C. (2020). Paracrine mechanisms of mesenchymal stromal cells in angiogenesis. Stem Cells International, 2020, 4356359. Advance online publication. https://doi.org/10.1155/2020/4356359

[35] Mastrolia, I., Foppiani, E. M., Murgia, A., Candini, O., Samarelli, A. V., Grisendi, G., Veronesi, E., Horwitz, E. M., & Dominici, M. (2019). Challenges in clinical development of mesenchymal stromal/stem cells: Concise review. Stem Cells Translational Medicine, 8(11), 1135–1148. https://doi.org/10.1002/sctm.19- 0044

[36] Mattei, V., & Delle Monache, S. (2024). Mesenchymal stem cells and their role in neurodegenerative diseases. Cells, 13(9), 779. https://doi.org/10.3390/cells13090779

[37] Mebarki, M., Abadie, C., Larghero, J., & Cras, A. (2021). Human umbilical cord-derived mesenchymal stem/stromal cells: A promising candidate for the development of advanced therapy medicinal products. Stem Cell Research & Therapy, 12(1), 152. https://doi.org/10.1186/s13287-021-02222-y

[38] Medina-Leyte, D. J., Domínguez-Pérez, M., Mercado, I., Villarreal-Molina, M. T., & Jacobo- Albavera, L. (2020). Use of human umbilical vein endothelial cells (HUVEC) as a model to study cardiovascular disease: A review. Applied Sciences (Basel, Switzerland), 10(3), 938. https://doi.org/10.3390/app10030938

[39] Mezey, É. (2022). Human mesenchymal stem/stromal cells in immune regulation and therapy. Stem Cells Translational Medicine, 11(2), 114–134. https://doi.org/10.1093/stcltm/szab020

[40] Musiał-Wysocka, A., Kot, M., & Majka, M. (2019). The pros and cons of mesenchymal stem cell-based therapies. Cell Transplantation, 28(7), 801–812. https://doi.org/10.1177/0963689719837897

[41] Noronha, N. C., Mizukami, A., Caliári-Oliveira, C., Cominal, J. G., Rocha, J. L. M., Covas, D. T., Swiech, K., & Malmegrim, K. C. R. (2019). Priming approaches to improve the efficacy of mesenchymal stromal cell-based therapies. Stem Cell Research & Therapy, 10(1), 131. https://doi.org/10.1186/s13287-019-1224-y

[42] Nowakowski, A., Walczak, P., Lukomska, B., & Janowski, M. (2016). Genetic engineering of mesenchymal stem cells to induce their migration and survival. Stem Cells International, 2016, 4956063. Advance online publication. https://doi.org/10.1155/2016/4956063

[43] Petrou, P., Kassis, I., Levin, N., Paul, F., Backner, Y., Benoliel, T., Oertel, F. C., Scheel, M., Hallimi, M., Yaghmour, N., Hur, T. B., Ginzberg, A., Levy, Y., Abramsky, O., & Karussis, D. (2020a). Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis. Brain, 143(12), 3574–3588. https://doi.org/10.1093/brain/awaa333

[44] Pirosa, A., Gottardi, R., Alexander, P. G., & Tuan, R. S. (2018). Engineering in-vitro stem cell-based vascularized bone models for drug screening and predictive toxicology. Stem Cell Research & Therapy, 9(1), 112. https://doi.org/10.1186/s13287-018-0847-8

[45] Qu, Q., Pang, Y., Zhang, C., Liu, L., & Bi, Y. (2020). Exosomes derived from human umbilical cord mesenchymal stem cells inhibit vein graft intimal hyperplasia and accelerate reendothelialization by enhancing endothelial function. Stem Cell Research & Therapy, 11(1), 133. https://doi.org/10.1186/s13287- 020-01639-1

[46] Schorn, L., Handschel, J., Lommen, J., VON Beck, F. P., Depprich, R., Kübler, N., & Holtmann, H. (2019). Evaluation of biocompatibility of different membrane surfaces using unrestricted somatic stem cells. In Vivo (Athens, Greece), 33(5), 1447–1454. https://doi.org/10.21873/invivo.11623

[47] Shafiee, S., Shariatzadeh, S., Zafari, A., Majd, A., & Niknejad, H. (2021). Recent advances on cell-based co-culture strategies for prevascularization in tissue engineering. Frontiers in Bioengineering and Biotechnology, 9, 745314. https://doi.org/10.3389/fbioe.2021.745314

[48] Shi, M. M., Yang, Q. Y., Monsel, A., Yan, J. Y., Dai, C. X., Zhao, J. Y., Shi, G. C., Zhou, M., Zhu, X. M., Li, S. K., Li, P., Wang, J., Li, M., Lei, J. G., Xu, D., Zhu, Y. G., & Qu, J. M. (2021). Preclinical efficacy and clinicalsafety of clinical-grade nebulized allogenic adipose mesenchymal stromal cells-derived extracellular vesicles. Journal of Extracellular Vesicles, 10(10), e12134. https://doi.org/10.1002/jev2.12134

[49] Song, N., Scholtemeijer, M., & Shah, K. (2020). Mesenchymal stem cell immunomodulation: Mechanisms and therapeutic potential. Trends in Pharmacological Sciences, 41(9), 653–664. https://doi.org/10.1016/j.tips.2020.06.009

[50] Sousa, A., Coelho, P., Leite, F., Teixeira, C., Rocha, A. C., Santos, I., Baylina, P., Fernandes, R., Soares, R., Costa, R., & Gomes, A. (2023). Impact of umbilical cord mesenchymal stromal/stem cell secretome and cord blood serum in prostate cancer progression. Human Cell, 36(3), 1160–1172. https://doi.org/10.1007/s13577-023-00880-z

[51] Szczepanik, E., Mierzewska, H., Antczak-Marach, D., Figiel-Dabrowska, A., Terczynska, I., Tryfon, J., Krzesniak, N., Noszczyk, B. H., Sawicka, E., Domanska-Janik, K., & Sarnowska, A. (2020). Intrathecal infusion of autologous adipose-derived regenerative cells in autoimmune refractory epilepsy: Evaluation of safety and efficacy. Stem Cells International, 2020, 7104243. https://doi.org/10.1155/2020/7104243

[52] Tesarova, L., Jaresova, K., Simara, P., & Koutna, I. (2020). Umbilical cord-derived mesenchymal stem cells are able to use bFGF treatment and represent a superb tool for immunosuppressive clinical applications. International Journal of Molecular Sciences, 21(15), 5366. https://doi.org/10.3390/ijms21155366

[53] Uzieliene, I., Urbonaite, G., Tachtamisevaite, Z., Mobasheri, A., & Bernotiene, E. (2018). The potential of menstrual blood-derived mesenchymal stem cells for cartilage repair and regeneration: Novel aspects. Stem Cells International, 2018, 5748126. https://doi.org/10.1155/2018/5748126

[54] Vieira Paladino, F., de Moraes Rodrigues, J., da Silva, A., & Goldberg, A. C. (2019). The immunomodulatory potential of Wharton’s jelly mesenchymal stem/stromal cells. Stem Cells International, 2019, 3548917. https://doi.org/10.1155/2019/3548917

[55] Wan Kamarul Zaman, W. S., & Abdullah, N. A. (Eds.). (2023). Sustainable material for biomedical engineering application. Springer Nature Singapore. https://doi.org/10.1007/978-981-99-2267-3

[56] Wiegner, R., Rudhart, N.-E., Barth, E., Gebhard, F., Lampl, L., Huber-Lang, M. S., & Brenner, R. E. (2018). Mesenchymal stem cells in peripheral blood of severely injured patients. European Journal of Trauma and Emergency Surgery, 44(4), 627–636. https://doi.org/10.1007/s00068-017-0849-8

[57] Xia, Y., Zhu, J., Yang, R., Wang, H., Li, Y., & Fu, C. (2023). Mesenchymal stem cells in the treatment of spinal cord injury: Mechanisms, current advances and future challenges. Frontiers in Immunology, 14, 1141601. https://doi.org/10.3389/fimmu.2023.1141601

[58] Yin, X., Nie, J., Nie, X., & Nie, Y. (2022). The relationship between nuclear factor-erythrocyterelated factor 2 and antioxidant enzymes in the placenta of patients with gestational diabetes and the metabolism of umbilical cord endothelial cells. Cellular and Molecular Biology, 68(12), 97–103. https://doi.org/10.14715/cmb/2022.68.12.18

[59] Yamashita, T., Kushida, Y., Abe, K., & Dezawa, M. (2021). Non-tumorigenic pluripotent reparative muse cells provide a new therapeutic approach for neurologic diseases. Cells, 10(4), 961. https://doi.org/10.3390/cells10040961

[60] Yu, S., Yu, S., Liu, H., Liao, N., & Liu, X. (2023). Enhancing mesenchymal stem cell survival and homing capability to improve cell engraftment efficacy for liver diseases. Stem Cell Research & Therapy, 14(1), 235. https://doi.org/10.1186/s13287-023-03476-4

[61] Zhu, H., Poon, W., Liu, Y., Leung, G. K.-K., Wong, Y., Feng, Y., Ng, S. C. P., Tsang, K. S., Sun, D. T. F., Yeung, D. K., Shen, C., Niu, F., Xu, Z., Tan, P., Tang, S., Gao, H., Cha, Y., So, K.-F., Fleischaker, R., . . . Young, W. (2016). Phase I-II clinical trial assessing safety and efficacy of umbilical cord blood mononuclear cell transplant therapy of chronic complete spinal cord injury. Cell Transplantation, 25(11), 1925–1943. https://doi.org/10.3727/096368916X691411

[62] Zhu, Y.-G., Shi, M.-M., Monsel, A., Dai, C.-X., Dong, X., Shen, H., Li, S.-K., Chang, J., Xu, C.-L., Li, P., Wang, J., Shen, M.-P., Ren, C.-J., Chen, D.-C., & Qu, J.-M. (2022). Nebulized exosomes derived from allogenic adipose tissue mesenchymal stromal cells in patients with severe COVID-19: A pilot study. Stem Cell Research & Therapy, 13(1), 220. https://doi.org/10.1186/s13287-022-02900-5