Tesis

Efek Pemberian Singkat Sekretom Sel Punca Mesenkim Asal Tali Pusat pada Darah Lengkap Pasien COVID-19 Derajat Berat terhadap Perubahan Sub Populasi Limfosit dan Ekspresi sPD-1 = Effect of Short Exposure Umbilical Cord Mesenchymal Stem Cells-derived Secretome to Whole Blood of Severe COVID-19 Patients on Changes in Lymphocytes Subpopulation and sPD-1 Expression.

Manifestasi klinis COVID-19 derajat berat ditandai dengan gejala pernapasan dan diperburuk komplikasi multi-organ pada pasien dengan komorbid. Imunitas selular, termasuk limfosit, merupakan salah satu faktor penentu keberhasilan tubuh melawan infeksi SARS-CoV-2. Namun disregulasi imun terjadi pada pasien COVID-19 derajat berat yang ditandai badai sitokin dan limfopenia. Pengobatan berbasis sel punca mesenkim (SPM) tengah diuji efektivitasnya dalam mengatasi COVID-19. Sebagai imunomodulator, efek terapeutik SPM serupa dengan sekretom yang dilepasnya. Studi ini bertujuan untuk menganalisis efek sekretom SPM asal tali pusat (SPM-TP) terhadap perubahan profil limfosit pada darah lengkap pasien COVID-19 derajat berat. Profil limfosit dikaji melalui analisis jumlah limfosit dengan teknik flow cytometry dan pengukuran parameter aktivasi fungsi limfosit, yaitu sPD-1. Jumlah limfosit pasien COVID-19 derajat berat menurun signifikan, terutama sel T dan NK, dibandingkan kontrol sehat, mengindikasikan limfopenia. Pemberian 3 μL sekretom dengan masa inkubasi 72 jam pada darah lengkap subjek COVID-19 derajat berat menunjukkan perbaikan imun, yaitu secara signifikan meningkatkan jumlah sel T CD4+ dan CD8+, meningkatkan ketahanan hidup sel B, dan meningkatkan kadar sPD-1. Peningkatan sPD-1 diduga dapat menurunkan kelelahan sel T terkait pemblokiran ikatan PD-1 ke PD-L1 oleh sPD-1.
Kata kunci: COVID-19, imun selular, limfosit, sekretom


Clinical manifestations of severe COVID-19 are characterized by respiratory symptoms and exacerbated multi-organ complications in patients with comorbidities. Cellular immunity, including lymphocytes, is a critical factor in combating SARS-CoV-2 infection. However, immune dysregulation occurs in severe COVID-19 patients characterized by cytokine storm and lymphopenia. Mesenchymal stem cells (MSCs)-based treatments are being tested for their effectiveness in treating COVID-19. As an immunomodulator, therapeutic effect of MSCs is similar to secretome it releases. This study aimed to analyze the effect of umbilical cord MSCs-derived (UC-MSCs) secretome on changes in lymphocytes profile in whole blood of severe COVID-19 patients. The lymphocytes profile was assessed by analyzing the number of lymphocytes using flow cytometry technique and measuring the parameters of lymphocytes function activation, sPD-1. The lymphocytes count of severe COVID-19 patients decreased significantly, especially T and NK cells, compared to healthy controls, indicating lymphopenia. 3 μL of secretome administration for 72 hours incubation on whole blood of severe COVID19 subjects showed immune improvement, which significantly increased CD4+ and CD8+ T cells count, increased B cell survival, and increased sPD-1 levels. An increase in sPD-1 is thought to decrease T cell exhaustion related to the blocking of PD-1 to PD-L1 ligation by sPD-1.
Keywords: COVID-19, cellular immunity, lymphocytes, secretome