Pengaruh Pemberian Eksosom Human Wharton Jelly Umbilical Cord-Mesenchymal Stem Cell (HWJUC-MSC) Terhadap Disfungsi Endotel dan Remodeling Vaskular pada Tikus Model Cedera Iskemia/Reperfusi Ginjal Periode Kronis

Rifki Habibi Rahman, Prof. Dr. dr. Dwi Cahyani Ratna Sari, M.Kes, PA(K).; dr. Junaedy Yunus, M.Sc, Ph.D.

2026 | Tesis | S2 Ilmu Kedokteran Dasar dan Biomedis

Latar Belakang: Cedera iskemia/reperfusi (I/R) adalah salah satu penyebab gagal ginjal akut yang dapat menyebabkan disfungsi endotel. Cedera I/R dengan periode reperfusi kronis dapat menginduksi remodeling vaskular dan angiogenesis. Eksosom dari Human Wharton Jelly Umbilical Cord-Mesenchymal Stem Cells (HWJUC-MSC) ditengarai memiliki efek renoprotektif pada model cedera I/R.

Tujuan: Penelitian ini bertujuan untuk mengkaji pengaruh pemberian eksosom HWJUC-MSC terhadap disfungsi endotel dan remodeling vaskular pada hewan coba model I/R ginjal periode kronis.

Metode: Sebanyak 26 ekor tikus Wistar jantan berusia 10-12 minggu dibagi menjadi lima kelompok: sham-operated (SO), kelompok I/R, dan tiga kelompok yang diberi eksosom HWJUC-MSC dosis rendah, sedang, dan tinggi. Kelompok I/R dan I/R + eksosom dilakukan operasi klem pediculus renalis bilateral selama 45 menit diikuti reperfusi. Eksosom disuntikkan melalui vena ekor pada hari pertama setelah operasi. Kreatinin serum diukur untuk analisis fungsi ginjal. Setelah 21 hari, hewan coba diterminasi. Ekspresi eNOS, VEGF, dan CD34 ginjal diukur menggunakan RT-PCR. Imunohistokimia CD34 dilakukan untuk menilai secara kualitatif morfologi kapiler peritubular. Ketebalan dinding dan lumen-wall area ratio (LWAR) arteri intrarenalis dinilai menggunakan pewarnaan Sirius Red diikuti analisis kuantitatif. Data dianalisis menggunakan One-Way ANOVA dengan post-hoc LSD.

Hasil: Eksosom dapat mempercepat pengembalian fungsi ginjal pada hari ke-21 setelah cedera I/R. Kelompok I/R + eksosom dosis tinggi menunjukkan ekspresi eNOS yang lebih tinggi dibandingkan kelompok I/R (p=0,02). Ekspresi VEGF dan CD34 lebih tinggi pada kelompok eksosom dosis tinggi dibandingkan kelompok I/R (p<0 p=0,03>

Kesimpulan: Eksosom HWJUC-MSC dapat mempercepat pemulihan fungsi ginjal, fungsi endotel, dan remodeling vaskular sehingga dapat menunjukkan efek renoprotektif.

Kata Kunci: cedera iskemia-reperfusi, eksosom, Wharton Jelly, disfungsi endotel, remodeling vaskular.

Backgrounds: Kidney ischemia/reperfusion (I/R) injury was one of the major cause of acute kidney injury that cause endothelial dysfunction. Prolonged injury promotes vascular remodeling and angiogenic responses. Exosomes from Human Wharton Jelly Umbilical Cord-Mesenchymal Stem Cells (HWJUC-MSC), have shown renoprotective effects in preclinical I/R models.

Objectives: This study aimed to explore the effects of HWJUC-MSC exosomes on endothelial dysfunction and vascular remodeling in prolonged kidney I/R.

Methods: Male 10-12 weeks Wistar rats (n=26) were equally grouped into 5: sham-operated (KSO), I/R group, and 3 groups treated with low-, medium-, and high-dose of HWJUC-MSC exosomes.  I/R and exosome groups were subjected to bilateral renal pedicle clamping for 45 minutes, followed by reperfusion. Exosomes were injected via tail vein on day-1 after clamping. Serum creatinine was obtained for functional analysis. After 21 days, all rats were sacrificed. Expression of renal eNOS, VEGF, and CD34 was measured using RT-PCR. Immunohistochemistry of CD34 was performed to qualitatively assess morphology of peritubular capillary. Wall thickness and lumen-wall area ratio (LWAR) of intrarenal arteries was assessed by Sirius Red staining followed by quantitative analysis. One-Way ANOVA with post-hoc LSD was used to analyze the data.

Results: Exosome enhanced functional recovery following kidney I/R at day 21. Group with high-dose exosome showed higher eNOS expression compared to I/R group (p=0.02). Kidney expression of VEGF and CD34 was higher in high-dose exosome group compared to I/R group (p<0 p=0.03>

Conclusions: HWJUC-MSC’s exosomes enhance renal functional recovery, endothelial function, and vascular remodeling indicating a dose-dependent renoprotective effect.

Keywords: ischemia-reperfusion injury, exosome, Wharton Jelly, endothelial dysfunction, vascular remodeling.

Kata Kunci : cedera iskemia-reperfusi, eksosom, Wharton Jelly, disfungsi endotel, remodeling vaskular