Sains Malaysiana 54(5)(2025): 1319-1330

http://doi.org/10.17576/jsm-2025-5405-10

Preclinical Safety Evaluation of WJMSCs and Their Secretome

(Penilaian Keselamatan Praklinikal WJMSC dan Sekretomnya)

PREMASANGERY KATHIVALOO^1,2,*, SUBRAMANI PARASURAMAN³, BADRUL AKMAL HISHAM MD YUSOFF⁴, RAZIANA RASIB¹, KARTHIK CHANDRAN¹ & KATHIRESANV.SATHASIVAM²

¹Meluha Therapeutics Sdn Bhd, Lot 1G-2G Kompleks Lanai, 62250 Putrajaya, Malaysia

²Department of Biotechnology, Faculty of Applied Sciences, AIMST University, Jalan Bedong-Semeling, 08100 Bedong, Kedah, Malaysia

³Unit of Pharmacology, Faculty of Pharmacy, AIMST University, Jalan Bedong-Semeling, 08100 Bedong, Kedah, Malaysia

⁴Department of Orthopedics & Traumatology, Faculty of Medicine, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia

Received: 5 July 2024/Accepted: 24 January 2025

Abstract

Mesenchymal stem cells (MSC) are a promising therapy in regenerative medicine due to their unique ability to differentiate into other cells. Among established sources of MSC, MSC derived from Wharton’s jelly (WJSC) of an umbilical cord is a popular source since it involves a painless procedure to obtain the cord with an exceptional proliferation rate compared to other sources. However, the safety and efficacy of MSC must be confirmed through preclinical studies before clinical trials in humans. A study was designed to achieve the maximum tolerable dose (MTD) and safety and toxicity effects of WJSC and its secretomes in animal models. The MTD was achieved through acute toxicity testing on healthy female Sprague Dawley (SD) rats while the safety was assessed using a subchronic toxicity study on healthy male and female SD rats divided into four groups (control, low dose, medium dose and high dose). The safety assessments were then evaluated through biochemical, haematological, and histopathological analyses where the data obtained were analysed using a one-way ANOVA followed by Tukey’s test. Statistical analysis confirmed no significant differences in all tests performed in the study groups. At the study's termination, neither cells nor secretomes injected rats were found to be deceased and no toxic or severe adverse effects were discovered. Thus, both WJSC and their secretomes applications in humans could be considered harmless for medical purposes.

Keywords: Acute toxicity; safety and efficacy; subchronic toxicity; Wharton’s jelly stem cells

Abstrak

Sel stem mesenkimal (MSC) merupakan terapi yang meyakinkan dalam perubatan regeneratif kerana keupayaan uniknya untuk membeza menjadi sel lain. Antara sumber MSC yang ada pada masa ini adalah MSC daripada jeli Wharton (WJSC) tali pusat yang merupakan sumber popular kerana mempunyai kadar percambahan yang lebih banyak berbanding sumber lain dan tidak melibatkan prosedur yang menyakitkan. Walau bagaimanapun, keselamatan dan keberkesanan MSC mesti disahkan melalui kajian praklinikal sebelum ujian klinikal pada manusia. Satu kajian telah direka untuk mencapai dos maksimum yang boleh diterima (MTD) dan kesan keselamatan dan ketoksikan WJSC dan sekretomnya dalam model haiwan. MTD dicapai melalui ujian toksisiti akut ke atas tikus Sprague Dawley (SD) betina yang sihat manakala keselamatan dinilai menggunakan kajian toksisiti subkronik ke atas tikus SD jantan dan betina sihat yang dibahagikan kepada empat kumpulan (kawalan, dos rendah, dos sederhana dan dos tinggi). Penilaian keselamatan kemudiannya dinilai melalui analisis biokimia, hematologi dan histopatologi dan data yang diperoleh dianalisis menggunakan ANOVA sehala diikuti dengan ujian Tukey. Analisis statistik mengesahkan tiada perbezaan yang signifikan dalam semua ujian yang dijalankan dalam kumpulan kajian. Pada pengakhiran kajian, tiada tikus yang disuntik dengan sel dan sekretom ditemui mati dan tiada kesan toksik atau kesan sampingan yang teruk ditemui. Oleh itu, kedua-dua aplikasi WJSC dan sekretom untuk manusia boleh dianggap tidak berbahaya untuk tujuan perubatan.

Kata kunci: Keselamatan dan keberkesanan; ketoksikan akut; ketoksikan subkronik; sel stem jeli Wharton

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*Corresponding author; email: kremasangery@gmail.com