Treatment of kidney failure with umbilical cord stem cells

Kidney disease is a common health problem. The World Health Organization has estimated that approximately 5 to 10 million people die annually from kidney diseases worldwide [1]. By 2040, it projected chronic kidney disease to be the fifth leading cause of death [2]. The number of patients with chronic renal failure is increasing, as well as the need for renal replacement therapies [3]. The etiology of this condition can be multifactorial, such as diabetes mellitus, glomerulonephritis, systemic infection, stone obstruction, hypertension, vasculitis, and renal dysplasia. Doctors treat end-stage chronic kidney failure with dialysis and kidney transplants. Hemodialysis cannot complete the excretion and metabolism of the kidney to maintain homeostasis and a series of other essential functions and can lead to many complications. Kidney transplants can completely replace kidney function, and the mortality rate is lower than dialysis patients, but there is a shortage of donor kidneys and long-term use of drugs. These therapies will place a heavy burden on patients’ financial and social aspects of life. Therefore, we need other alternatives in the management of kidney disease to prevent the progression to end-stage kidney disease.

The main therapies for chronic kidney failure are dialysis and kidney transplantation.

Current treatments to prolong the life of end-stage renal disease patients are limited to renal replacement therapy, dialysis, or renal transplantation [4]. Because of the high medical costs associated with dialysis therapy, which also affects the patient’s quality of life, dialysis is not an ideal solution. This is mainly because dialysis does not restore or replace all kidney functions. Meanwhile, the severe shortage of organ donors and the potential risk of organ rejection have limited the practice of kidney transplantation [5]. Therefore, exploring new treatments that improve a patient’s quality of life and possibly cure, reverse, or ease kidney disease is important. Stem cell therapy has opened new doors for patients with kidney disease.

Kidney failure treatment using mesenchymal stem cells.

Stem cells have interested researchers because of the combination of two unique properties [6]. First, with specific treatment, they are capable of prolonged self-renewal through division. Second, controlled physiological exposure can influence their differentiation into specific cell lines. Thus, stem cells create hope for individuals with many conditions through their ability to repair and regenerate diseased tissues. Mesenchymal stem cells (MSCs) secrete several growth factors and cytokines to regulate neighboring parenchymal cells, activating tissue regeneration. However, the true therapeutic potential of stem cells is still unknown. Issues that need to be resolved include: (1) The best way to get cells (2) How to improve the functional integration of transplanted cells?

MSCs are the major source of cell therapy because of their ability to differentiate into many cell types, adipose tissue, and connective tissue. It can easily proliferate these cells in the laboratory and can maintain their ability to regenerate after cryopreservation. These properties make MSCs a prime candidate for various therapeutic applications. In recent years, experimental studies have uncovered the potential of MSCs to improve kidney function in several chronic kidney disease models, and several clinical studies have shown safety and effectiveness in chronic kidney disease [6]. Many studies have showed that MSCs can differentiate into kidney cells or specifically into kidney component cells, such as kidney epithelial cells, mesodermal cells, and endothelial cells [7-10].

Kidney disease treatment using umbilical cord mesenchymal stem cells.

The source of stem cells is the human umbilical cord, which has a lot of potential for therapies and stem cell banking. Umbilical cord mesenchymal stem cells have more tremendous advantages than stem cells taken from bone marrow and adipose tissue regarding cell isolation and culture time. Studies in animal models have shown improvement in kidney disease through various mechanisms [11]. I have not conducted human studies involving human umbilical cord mesenchymal stem cells to treat kidney disease on a large scale, but MSC therapy appears to be safe. Rahyussalim and colleagues used human umbilical cord mesenchymal stem cells intradermally and intravenously in patients previously diagnosed with spinal myelitis with comorbid chronic kidney disease [12]. This article reported improvements in patient movement and kidney function. Deng and colleagues conducted a study to evaluate the effectiveness of human umbilical cord mesenchymal stem cells on lupus nephritis [13]. Currently, human umbilical cord mesenchymal stem cells are used to treat lupus nephritis and systemic lupus erythematosus. The researchers administered 120 million umbilical cord-derived mesenchymal stem cells intravenously to patients with renal failure, and they followed up with them for six months [14]. It reported no side effects during or after medication administration or at any follow-up visits. Creatinine levels decreased and remained normal for six months after treatment. Using umbilical cord-derived mesenchymal stem cells is safe, well-tolerated, and beneficial for patients with kidney disease.

Advances and prospects of stem cell therapy for kidney diseases

The challenges in developing stem cell treatment technology from the laboratory to widespread clinical application remain and are being optimized by researchers. The success of cell-based therapy could expand regenerative medicine’s scope in the future. Once fully tested, enhanced stem cells could become an important new tool for current and unexplored treatment areas. Stem cells have promising potential as a form of regenerative medicine for kidney diseases.

References:

1. Luyckx, Valerie A., Marcello Tonelli, and John W. Stanifer. “The global burden of kidney disease and the sustainable development goals.” Bulletin of the World Health Organization96, no. 6 (2018): 414.
2. Luyckx, Valerie A., Ziyad Al-Aly, Aminu K. Bello, Ezequiel Bellorin-Font, Raul G. Carlini, June Fabian, Guillermo Garcia-Garcia et al. “Sustainable development goals relevant to kidney health: an update on progress.” Nature Reviews Nephrology17, no. 1 (2021): 15-32.
3. Nahas, Meguid EL. “The global challenge of chronic kidney disease.” Kidney international68, no. 6 (2005): 2918-2929.
4. Liyanage, Thaminda, Toshiharu Ninomiya, Vivekanand Jha, Bruce Neal, Halle Marie Patrice, Ikechi Okpechi, Ming-hui Zhao et al. “Worldwide access to treatment for end-stage kidney disease: a systematic review.” The Lancet385, no. 9981 (2015): 1975-1982.
5. Saidi, R. F., and SK Hejazii Kenari. “Challenges of organ shortage for transplantation: solutions and opportunities.” International journal of organ transplantation medicine5, no. 3 (2014): 87.
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7. Herrera, Maria Beatriz, Benedetta Bussolati, Stefania Bruno, Valentina Fonsato, Giuseppe Mauriello Romanazzi, and Giovanni Camussi. “Mesenchymal stem cells contribute to the renal repair of acute tubular epithelial injury.” International journal of molecular medicine14, no. 6 (2004): 1035-1041.
8. Bussolati, Benedetta, Peter V. Hauser, Raquel Carvalhosa, and Giovanni Camussi. “Contribution of stem cells to kidney repair.” Current stem cell research & therapy4, no. 1 (2009): 2-8.
9. Wong, Chee-Yin, Yao-Ming Chang, Yu-Shuen Tsai, Wailap Victor Ng, Soon-Keng Cheong, Ting-Yu Chang, I. Chung, and Yang-Mooi Lim. “Decoding the differentiation of mesenchymal stem cells into mesangial cells at the transcriptomic level.” BMC genomics21, no. 1 (2020): 1-14.
10. Wang, Chengen, Yuan Li, Min Yang, Yinghua Zou, Huihui Liu, Zeyin Liang, Yue Yin, Guochen Niu, Ziguang Yan, and Bihui Zhang. “Efficient differentiation of bone marrow mesenchymal stem cells into endothelial cells in vitro.” European Journal of Vascular and Endovascular Surgery55, no. 2 (2018): 257-265.
11. Li, Wen, Li Wang, Xiaoqian Chu, Huantian Cui, and Yuhong Bian. “Icariin combined with human umbilical cord mesenchymal stem cells significantly improve the impaired kidney function in chronic renal failure.” Molecular and cellular biochemistry428, no. 1 (2017): 203-212.
12. Rahyussalim, Ahmad Jabir, Ifran Saleh, Tri Kurniawati, and Andi Praja Wira Yudha Lutfi. “Improvement of renal function after human umbilical cord mesenchymal stem cell treatment on chronic renal failure and thoracic spinal cord entrapment: a case report.” Journal of medical case reports11, no. 1 (2017): 1-7.
13. Deng, DanQi, Peilian Zhang, Yun Guo, and Teck Onn Lim. “A randomised double-blind, placebo-controlled trial of allogeneic umbilical cord-derived mesenchymal stem cell for lupus nephritis.” Annals of the Rheumatic Diseases76, no. 8 (2017): 1436-1439.
14. Riordan, Neil H., Richard A. Ambrozic, and Jorge Paz-Rodríguez. “Case report: effect of umbilical cord mesenchymal stem cells on immunoglobulin A nephropathy after acute renal failure.” American Journal of Translational Research 14, no. 7 (2022): 4855.