Allogeneic bone marrow mesenchymal stem cell-derived exosomes alleviate human hypoxic AKI-on-a-Chip within a tight treatment window

Abstract Background Acute hypoxic proximal tubule (PT) injury and subsequent maladaptive repair present high mortality and increased risk of acute kidney injury (AKI) - chronic kidney disease (CKD) transition. Human bone marrow mesenchymal stem cell-derived exosomes (hBMMSC-Exos) as potential cell therapeutics can be translated into clinics if drawbacks on safety and efficacy are clarified. Here, we determined the real-time effective dose and treatment window of allogeneic hBMMSC-Exos, evaluated their performance on the structural and functional integrity of 3D microfluidic acute hypoxic PT injury platform. Methods hBMMSC-Exos were isolated and characterized. Real-time impedance-based cell proliferation analysis (RTCA) determined the effective dose and treatment window for acute hypoxic PT injury. A 2-lane 3D gravity-driven microfluidic platform was set to mimic PT in vitro. ZO-1, acetylated α-tubulin immunolabelling, and permeability index assessed structural; cell proliferation by WST-1 measured functional integrity of PT. Results hBMMSC-Exos induced PT proliferation with ED50 of 172,582 µg/ml at the 26th hour. Hypoxia significantly decreased ZO-1, increased permeability index, and decreased cell proliferation rate on 24–48 h in the microfluidic platform. hBMMSC-Exos reinforced polarity by a 1.72-fold increase in ZO-1, restored permeability by 20/45-fold against 20/155 kDa dextran and increased epithelial proliferation 3-fold compared to control. Conclusions The real-time potency assay and 3D gravity-driven microfluidic acute hypoxic PT injury platform precisely demonstrated the therapeutic performance window of allogeneic hBMMSC-Exos on ischemic AKI based on structural and functional cellular data. The novel standardized, non-invasive two-step system validates the cell-based personalized theragnostic tool in a real-time physiological microenvironment prior to safe and efficient clinical usage in nephrology

Additional file 1 of Allogeneic bone marrow mesenchymal stem cell-derived exosomes alleviate human hypoxic AKI-on-a-Chip within a tight treatment window

Supplementary Material

Histology Laboratory Guide Book

Histology and Embryology education and research are fundamental cornerstones of medical science. Histology, which is the basis of many fields of preclinical and clinical medicine, defines the visual components of cells, tissues and organs at the microscope level. This book, which we have published in the third extended version, provides students with a selection of micrographs created from archive preparations that Hacettepe University Faculty of Medicine Department of Histology and Embryology has been carefully created for more than 50 years. This selection has been prepared with the common effort of our academic staff, research assistants and technicians. The purpose of the book is to guide medical and health sciences students while examining the original preparations under the microscope in the laboratory, to match the functional properties associated with the structure of healthy cells with histochemical staining properties. Each chapter in the book contains brief information of micrographs on the basis of organs, tissues and cells under the relevant technical title. In this edition; we would respectfully like to thank the founder of our department and the first woman dean of medical school of our country, Prof. İlhan Kerse and, all of our retired professors who greatly contributed to our education by showing us the way of science. We also thank our former heads of department Prof. Ülken Örs, Prof. Esin Aşan, Prof. Ayşe Nur Çakar, Prof. Attila Dağdeviren, Prof. Sevda Fatma Müftüoğlu and Prof. Fevziye Figen Kaymaz. On behalf of our department, we wish all our students sincere success.Histoloji ve Embriyoloji, tıp biliminin vazgeçilmez temel taşlarından birisini oluşturur. Tıbbın birçok preklinik ve klinik alanına esas oluşturan histoloji, hücre, doku ve organların mikroskop düzeyinde görsel bileşenlerini tanımlar. Beşinci genişletilmiş basımını yaptığımız bu kitap, Hacettepe Üniversitesi Tıp Fakültesi Histoloji ve Embriyoloji Anabilim Dalı’nın 50 yılı aşkın süredir özenle oluşturduğu arşiv preparatlarından derlenmiş mikrograf seçkisini öğrencilere sunmaktadır. Bu seçki, anabilim dalımız öğretim üyeleri, araştırma görevlileri ve teknisyenlerinin ortak emeği ile hazırlanmıştır. Kitabın amacı; tıp ve sağlık bilimleri öğrencilerine laboratuvarda bu preparatları mikroskop altında incelerken rehberlik etmek, sağlıklı hücrelerin yapıları ile ilişkili işlevsel özelliklerini, histokimyasal boyanma özellikleriyle eşleştirmelerini sağlamaktır. Kitaptaki her bölüm, ilgili teknik başlık ya da sisteme ait preparat mikrografları hakkında organ, doku, hücre temelinde kısa bilgiler vermektedir. Bu baskıda; anabilim dalımızın kurucusu ve ülkemizin ilk kadın tıp fakültesi dekanı Sn. Prof. Dr. İlhan Kerse başta olmak üzere, bizlere bilimin yolunu göstererek yetişmemize katkıda bulunan anabilim dalı başkanlarımız Sn. Prof. Dr. Ülken Örs, Sn. Prof. Dr. Esin Aşan, Sn. Prof. Dr. Ayşe Nur Çakar, Sn. Prof. Dr. Attila Dağdeviren, Sn. Prof. Dr. Sevda Fatma Müftüoğlu, Sn. Prof. Dr. Fevziye Figen Kaymaz’a ve tüm emekli hocalarımıza teşekkür ediyoruz. Anabilim dalımız adına tüm öğrencilerimize içten başarı dileklerimizle