Sains Malaysiana 51(2)(2022): 577-583

http://doi.org/10.17576/jsm-2022-5102-21

Human Umbilical Cord Mesenchymal Stem Cells Inhibit Coronary Artery Injury in Mice with Lactobacillus casei Wall Extract-Induced Kawasaki Disease

(Sel Stem Mesenkima Tali Pusat Manusia Menghalang Kecederaan Arteri Koronari pada Tikus dengan Penyakit Kawasaki yang Disebabkan oleh Ekstrak Dinding Lactobacillus casei)

HUA GUO¹, FUYONG JIAO², XIAOYONG ZHANG³, YANGMENG FENG⁴, YANG LIU⁴, DAOYAN LIANG¹, XIAOHUA YAN² & HAIXIANG ZHANG⁴*

¹Clinical Laboratory of Shaanxi Provincial People's Hospital, Xi’an 710068, China

²Children's Hospital of Shaanxi Provincial People's Hospital, Xi’an 710068, China

³The First Affiliated Hospital of Xi'an Medical University, Xi’an 710077, China

⁴Shaanxi Engineering Research Center of Cell Immunology, Central Laboratory of Shaanxi Provincial People's Hospital, Xi’an 710068, China

Received: 22 March 2021/Accepted: 2 July 2021

ABSTRACT

Kawasaki disease (KD) is a serious threat to children’s physical and mental health. This study investigated the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on KD coronary arteritis induced by Lactobacillus casei wall extract (LCWE) in an animal model. Sixty BALB/C mice were randomly assigned to three groups (n = 20 mice per group). Mice in the model and stem-cell groups were injected with LCWE, while the control-group mice were injected with phosphate-buffered saline (PBS) for 2 days. At day 16 of modeling, PBS was injected into the control and model-group mice, and hUC-MSCs were injected into the stem-cell group mice for 10 days. At days 4, 15, 26, and 32 of modeling, echocardiography and histopathology were performed to examine the cardiac structure and the morphological changes in the coronary arteries in each group. B-ultrasonography showed that 57.5% (23/40) of the mice had coronary artery lesions, of which 5% (2/40) had right coronary artery aneurysm, 27.5% (11/40) had coronary artery wall thickening, a widened inner diameter of the main artery of the left coronary artery, and thickened intima. Histopathology showed slight swelling of the epicardium of the aortic valve, mitral valve, right ventricle, and atrium, as well as scattered infiltration of a few neutrophils. Following hUC-MSCs intervention treatment, B-ultrasonography showed a decrease in the main coronary artery diameter, while histopathology showed no obvious vascular inflammatory reaction or other obvious abnormalities. These findings highlight that hUC-MSCs inhibit coronary artery injury in animal models of KD induced by LCWE.

Keywords: Coronary artery; human umbilical cord mesenchymal stem cells; Kawasaki disease; Lactobacillus casei wall extract

ABSTRAK

Penyakit Kawasaki (KD) adalah ancaman serius kepada kesihatan fizikal dan mental kanak-kanak. Kajian ini mengkaji kesan sel stem mesenkima tali pusat manusia (hUC-MSCs) pada arteritis koronari KD yang disebabkan oleh ekstrak dindingLactobacillus casei (LCWE) dalam model haiwan. Enam puluh tikus BALB/C secara rawak diberikan kepada tiga kumpulan (n = 20 tikus setiap kumpulan). Tikus dalam model dan kumpulan sel stem telah disuntik dengan LCWE, manakala tikus kumpulan kawalan disuntik dengan garam penampan fosfat (PBS) selama 2 hari. Pada hari ke-16 pemodelan, PBS disuntik ke dalam tikus kawalan dan kumpulan model dan hUC-MSC disuntik ke dalam tikus kumpulan sel stem selama 10 hari. Pada hari 4, 15, 26 dan 32 pemodelan, ekokardiografi dan histopatologi dilakukan untuk memeriksa struktur jantung dan perubahan morfologi dalam arteri koronari dalam setiap kumpulan. B-ultrasonografi menunjukkan bahawa 57.5% (23/40) daripada tikus mempunyai lesi arteri koronari dengan 5% (2/40) mempunyai aneurisma arteri koronari kanan, 27.5% (11/40) mempunyai penebalan dinding arteri koronari, diameter dalaman arteri utama arteri koronari kiri melebar dan intima yang menebal. Histopatologi menunjukkan sedikit pembengkakan epikardium injap aorta, injap mitral, ventrikel kanan dan atrium, serta penyusupan bertaburan beberapa neutrofil. Berikutan rawatan intervensi hUC-MSCs, B-ultrasonografi menunjukkan penurunan dalam diameter arteri koronari utama, manakala histopatologi tidak menunjukkan tindak balas keradangan vaskular yang jelas atau keabnormalan lain yang jelas. Penemuan ini menyerlahkan bahawa hUC-MSC menghalang kecederaan arteri koronari dalam model haiwan KD yang disebabkan oleh LCWE.

Kata kunci: Arteri koronari; ekstrak dinding Lactobacillus casei; penyakit Kawasaki; sel stem mesenkima tali pusat manusia

REFERENCES

Abbaszadeh, H., Ghorbani, F., Derakhshani, M., Movassaghpour, A. & Yousefi, M. 2020. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles: A novel therapeutic paradigm. Journal of Cellular Physiology 235(2): 706-717.

Arutyunyan, I., Elchaninov, A., Makarov, A. & Fatkhudinov, T. 2016. Umbilical cord as prospective source for mesenchymal stem cell-based therapy. Stem Cells International 2016: 6901286.

Dallaire, F., Fortier-Morissette, Z., Blais, S., Dhanrajani, A., Basodan, D., Renaud, C., Mathew, M., De Souza, A.M., Dionne, A., Blanchard, J., Saulnier, H., Kaspy, K., Rached-d'Astous, S., Dahdah, N., McCrindle, B.W., Human, D.G. & Scuccimarri, R. 2017. Aspirin dose and prevention of coronary abnormalities in Kawasaki disease. Pediatrics 139(6): e20170098.

Dou, J., Li, H., Sun, L., Yan, W., Lv, H. & Ding, Y. 2013. Histopathological and ultrastructural examinations of rabbit coronary artery vasculitis caused by bovine serum albumin: An animal model of Kawasaki disease. Ultrastructural Pathology 37(2): 139-145.

Kim, H.J., Kim, J.J., Yun, S.W., Yu, J.J., Yoon, K.L., Lee, K.Y., Kil, H.R., Kim, G.B., Han, M.K., Song, M.S., Lee, H.D., Ha, K.S., Hong, Y.M., Jang, G.Y., Lee, J.K. & Korean Kawasaki Disease Genetics Consortium. 2020. Association of the IL16 Asn1147Lys polymorphism with intravenous immunoglobulin resistance in Kawasaki disease. Journal of Human Genetics 65(4): 421-426.

Li, L., Jaiswal, P.K., Makhoul, G., Jurakhan, R., Selvasandran, K., Ridwan, K. & Cecere, R. 2017. Hypoxia modulates cell migration and proliferation in placenta-derived mesenchymal stem cells. Journal of Thoracic and Cardiovascular Surgery 154(2): 543-552.

Lo, M.S. 2020. A framework for understanding Kawasaki disease pathogenesis. Clinical Immunology 214: 108385.

Lo, M.S. & Newburger, J.W. 2018. Role of intravenous immunoglobulin in the treatment of Kawasaki disease. International Journal of Rheumatic Diseases 21(1): 64-69.

Matundan, H.H., Sin, J., Noval Rivas, M., Fishbein, M.C., Lehman, T.J., Chen, S., Gottlieb, R.A., Crother, T.R., Abe, M. & Arditi, M. 2019. Myocardial fibrosis after adrenergic stimulation as a long-term sequela in a mouse model of Kawasaki disease vasculitis. JCI Insight 4(3): e126279.

Muheremu, A., Sun, J.G., Wang, X.Y., Zhang, F., Ao, Q. & Peng, J. 2016. Combined use of Y-tube conduits with human umbilical cordstem cells for repairing nerve bifurcation defects. Neural Regeneration Research 11(4): 664-669.

Nakayama, Y., Komatsu, J., Nishimura, Y., Fujita, T. & Doi, Y.L. 2020. Kawasaki disease: Acute myocardial infarction of adult-onset associated with a giant coronary artery aneurysm. Journal of the American College of Cardiology 75(11_Supplement_1): 2362.

Noval Rivas, M., Lee, Y., Wakita, D., Chiba, N., Dagvadorj, J., Shimada, K., Chen, S., Fishbein, M.C., Lehman, T.J., Crother, T.R. & Arditi, M. 2017. CD8+ T cells contribute to the development of coronary arteritis in the Lactobacillus casei cell wall extract-induced murine model of Kawasaki disease. Arthritis & Rheumatology 69(2): 410-421.

Perea-Gil, I., Monguió-Tortajada, M., Gálvez-Montón, C., Bayes-Genis, A., Borràs, F.E. & Roura, S. 2015. Preclinical evaluation of the immunomodulatory properties of cardiac adipose tissue progenitor cells using umbilical cord blood mesenchymal stem cells: A direct comparative study. BioMed Research International 2015: 439808.

Qin, L.J., Niu, M.Z., Wang, H.W., Shi, H. & Cheng, P.X. 2006. Experimental study on coronary arteritis induced by immunization of mice with Lactobacillus casei cell wall extract. Journal of Applied Clinical Pediatrics 21(20): 1388-1391.

Sasawatari, S., Okamoto, Y., Kumanogoh, A. & Toyofuku, T. 2020. Blockade of N-Glycosylation promotes antitumor immune response of T cells. Journal of Immunology 204(5): 1373-1385.

Suganuma, E., Sato, S., Honda, S. & Nakazawa, A. 2020. A novel mouse model of coronary stenosis mimicking Kawasaki disease induced by Lactobacillus casei cell wall extract. Experimental Animals 69(2): 233-241.

Suzuki, E., Fujita, D., Takahashi, M., Oba, S. & Nishimatsu, H. 2017. Therapeutic effects of mesenchymal stem cell-derived exosomes in cardiovascular disease. Advances in Experimental Medicine and Biology 998: 179-185.

Tanaka, H., Yanai, C., Miura, N.N., Ishibashi, K., Yamanaka, D., Ohnishi, H., Ohno, N. & Adachi, Y. 2020. Coronary vasculitis induced in mice by cell wall mannoprotein fractions of clinically isolated Candida species. Medical Mycology Journal 61(3): 33-48.

Uchimura, R., Ueda, T., Fukazawa, R., Hayakawa, J., Ohashi, R., Nagi-Miura, N., Ohno, N., Migita, M. & Itoh, Y. 2020. Adipose tissue-derived stem cells suppress coronary arteritis of Kawasaki disease in vivo. Pediatrics International 62(1): 14-21.

Yan, J.R., Xie, L.J., Wang, J.Y., Xiao, T.T. & Huang, M. 2012. Mice model of coronary artery lesion induced by Candida albicans water soluble fraction. Journal of Clinical Pediatric 30(2): 172-178.

*Corresponding author; email: 307706698@qq.com