Electronic Theses and Dissertation

ABSTRAK

Latar Belakang: Epilepsi merupakan gangguan neurologis kronis yang ditandai oleh kejang berulang, degenerasi neuron, dan gangguan fungsi kognitif. Meskipun obat anti-kejang efektif mengendalikan kejang, terapi tersebut belum mampu mencegah epileptogenesis maupun memulihkan fungsi neuron. Human umbilical cord-derived mesenchymal stem cells (hUMSC) beserta produk turunannya, yaitu sekretom dan eksosom, berpotensi sebagai terapi regeneratif. Penelitian ini bertujuan membandingkan efektivitas terapi hUMSC, sekretom, dan eksosom pada model tikus epilepsi yang diinduksi pilokarpin.
Metode: Penelitian eksperimental ini menggunakan rancangan randomized controlled post-test-only design pada tikus jantan galur Wistar. Penelitian terdiri atas dua tahap, yaitu pilot study untuk menentukan dosis optimal pilokarpin dengan mortalitas minimal dan main study yang melibatkan lima kelompok, yaitu kontrol sehat, epilepsi tanpa terapi, epilepsi dengan terapi hUMSC, sekretom, dan eksosom. Epilepsi diinduksi melalui pemberian pilokarpin secara intraperitoneal. Terapi hUMSC, sekretom, dan eksosom diberikan secara intravena pada hari ke-14, ke-28, dan ke-42 pascainduksi. Efektivitas terapi dievaluasi melalui uji Morris Water Maze, pemeriksaan histopatologi hipokampus, serta analisis ekspresi gen synaptic vesicle glycoprotein 2A (SV2A) dan SRY-box transcription factor 10 (SOX10) menggunakan quantitative polymerase chain reaction (qPCR).
Hasil: Terapi hUMSC secara signifikan menurunkan kerusakan neuron hipokampus, meningkatkan ekspresi SV2A dan SOX10 hingga mendekati kelompok kontrol sehat, serta memperbaiki kemampuan pembelajaran spasial dibandingkan kelompok epilepsi tanpa terapi, sekretom, dan eksosom (p < 0,05). Terapi sekretom memberikan perbaikan dengan tingkat efektivitas sedang, sedangkan terapi eksosom menunjukkan manfaat terapeutik yang terbatas.
Kesimpulan: Terapi hUMSC memberikan efek neuroprotektif, molekuler, dan kognitif yang lebih unggul dibandingkan terapi sekretom maupun eksosom, sehingga berpotensi menjadi strategi terapi regeneratif pada epilepsi.

Kata Kunci: eksosom, epilepsi, fungsi kognitif, hUMSC, neuroproteksi, sekretom, stem cell, terapi regeneratif saraf

ABSTRACT Background: Epilepsy is a chronic neurological disorder characterized by recurrent seizures, neuronal degeneration, and cognitive impairment. Although current antiseizure medications effectively control seizures, they do not prevent epileptogenesis or restore neuronal function. Human umbilical cord-derived mesenchymal stem cells (hUMSCs) and their cell-free derivatives, including secretome and exosomes, have emerged as promising regenerative therapies. This study compared the therapeutic efficacy of HuMSCs, secretome, and exosomes in a pilocarpine-induced rat model of epilepsy. Methods: This experimental study employed a randomized controlled post-test-only design using male Wistar rats. The study was conducted in two phases: a pilot study to establish the optimal pilocarpine dose for epilepsy induction with minimal mortality, followed by a main study comprising five groups: healthy control, untreated epilepsy, hUMSC-treated epilepsy, secretome-treated epilepsy, and exosome-treated epilepsy. Epilepsy was induced by intraperitoneal administration of pilocarpine. Treatments with hUMSC, secretome and exosome were administered intravenously on days 14, 28, and 42 after induction. Therapeutic efficacy was assessed by the Morris Water Maze, histopathological evaluation of the hippocampus, and quantitative polymerase chain reaction analysis of synaptic vesicle glycoprotein 2A (SV2A) and SRY-box transcription factor 10 (SOX10) gene expression. Results: HuMSC therapy significantly reduced hippocampal neuronal damage, restored SV2A and SOX10 expression to levels comparable with healthy controls, and improved spatial learning compared with untreated, secretome-, and exosome-treated groups (p < 0.05). Secretome produced moderate therapeutic effects, whereas exosomes demonstrated limited efficacy. Conclusion: HuMSC therapy conferred superior neuroprotective, molecular, and cognitive benefits compared with secretome and exosome therapy, supporting its potential as a regenerative treatment strategy for epilepsy. Keywords: cognitive function, epilepsy, exosomes, human umbilical cord mesenchymal stem cells (hUMSC), neuroprotection, neuroregenerative therapy, secretome.