Pengaruh Pemberian Eksosom Human's Wharton Jelly Umbilical Cord Mesenchymal Stem Cells Terhadap Faktor Neurotropik Pada Tikus Model Iskemia Serebral Global Transien

Dimas Satrio Wicaksono, dr. Nur Arfian, Ph.D ; dr. Ratih Yuniartha, Ph.D

2025 | Tesis | S2 Ilmu Kedokteran Dasar dan Biomedis

Latar Belakang : Stroke merupakan penyebab kematian kedua di dunia dengan  tingkat mortalitas 5,5 juta, dan 50% penyintas stroke hidup dengan disabilitas.  Indonesia mempunyai angka mortalitas dan DALYs tertinggi akibat stroke di Asia Tenggara. Cedera iskemik akibat stroke dapat menyebabkan penurunan faktor  neurotropik salah satunya BDNF/TrkB dan NGF. Terapi Eksosom menjadi salah satu pilihan terapi stroke, contohnya eksosom Human’s Wharton Jelly Umbilical Cord-Mesenchymal Stem Cells. Eksosom dengan aksinya sebagai pembawa dan komunikasi antar sel berpotensi memberikan pengaruh anti inflamasi dan meningkatkan faktor neurotropik 

Tujuan : Tujuan penelitian ini adalah mengkaji pengaruh pemberian eksosom terhadap sebaran sel positif  CD68 dan gen faktor neurotropik mRNA BDNF, TrkB, dan NGF pada lobus frontal tikus model stroke iskemia serebral global transien 

Metode : Penelitian ini menggunakan subjek penelitian berupa tikus Wistar jantan usia 12-14 minggu dengan berat badan awal 250-350g berjumlah 24 ekor tikus 

dengan model iskemia serebral global transien dengan induksi BCCAO. Terdapat 5 kelompok yaitu: SO, BC, EXO1 (dosis eksosom 8,5x104 partikel/ekor), EXO2 (8,5x105 partikel/ekor), dan EXO3 (8,5x106 partikel/ekor). Evaluasi pemberian terapi pada tikus dinilai melalui deskripsi histologi pewarnaan imunohistokimia (IHC) CD68 pada lapisan III; penilaian ekspresi mRNA BDNF, TrkB, dan NGF

Hasil : Melalui pemeriksaan IHC, tampak ekspresi protein CD68 kelompok EXO3 lebih rendah dibandingkan kelompok BCCAO. Ekspresi protein CD68 EXO3 tampak lebih rendah dibandingkan kelompok EXO1 dan EXO2. Pada kelompok EXO3 memiliki ekspresi mRNA BDNF (p = 0,009), TrkB (p = 0,03 ), dan NGF (p < 0>

Kesimpulan :  Eksosom mempunyai potensi terapi tambahan pada kasus model iskemia serebral glabal transien. Potensi antiinflamasi dan neuroprotektif ditunjukan melalui penurunan ekspresi sitokin proinflamasi, penurunan aktivitas mikroglia, dan peningkatkan faktor neurotropik

Background: Stroke is the second leading cause of death worldwide, with a mortality rate of 5,5 million, and 50% of stroke survivors live with disabilities. Indonesia has the highest mortality rate and disability-adjusted life years (DALYs) due to stroke in Southeast Asia. Ischemic injury caused by stroke can lead to a decrease in neurotrophic factors, including BDNF/TrkB and NGF. Exosome therapy has emerged as a potential treatment for stroke, such as exosomes derived from Human Wharton’s Jelly Umbilical Cord-Mesenchymal Stem Cells. With their role in intercellular communication and cargo delivery, exosomes have the potential to exert anti-inflammatory effects and enhance neurotrophic factors. 

Objective: This study aims to investigate the effect of exosome administration on the distribution of CD68 positive cell and the neurotrophic factor mRNA genes BDNF, TrkB, and NGF in the frontal lobe of a transient global cerebral ischemia rat model. 

Methods: This study used 24 male Wistar rats aged 12–14 weeks with an initial body weight of 250–350g, subjected to a transient global cerebral ischemia model induced by BCCAO. The subjects were divided into five groups: SO, BCCAO, EXO1 (exosome dose of 8,5×10? particles/rat), EXO2 (8,5×10? particles/rat), and EXO3 (8,5×10? particles/rat). The therapeutic evaluation was conducted through histological analysis using immunohistochemistry (IHC) staining of CD68 in layer III and assessment of mRNA expression levels of BDNF, TrkB, and NGF. 

Results: IHC analysis showed that CD68 protein expression in the EXO3 group was lower than in the BCCAO group. CD68 expression in the EXO3 group was also lower than in the EXO1 and EXO2 groups. The EXO3 group exhibited higher mRNA expression levels of BDNF (p = 0,009), TrkB (p = 0,03), and NGF (p < 0>

Conclusion: Exosomes have potential as an adjunct therapy for transient global cerebral ischemia models. Their anti-inflammatory and neuroprotective properties are demonstrated through the reduction of pro-inflammatory cytokine expression, decreased microglial activity, and increased neurotrophic factors. 

Kata Kunci : Iskemia serebral global, eksosom, neuroinflamasi, faktor neurotropik