Decellularization and Recellularization of Natural, Benign Prostatic Hyperplasia and Malignant Human Prostatic Tissues: Role of Extracellular Matrix Behavior on Development of Prostate Cancer Publisher



Kajbafzadeh AM¹ ; Jafarnezhadansariha F¹ ; Sharifi SHH¹ ; Sabetkish S¹ ; Parvin M² ; Tabatabaei S³ ; Fendereski K¹ ; Akbarzadeh A¹ ; Ladiseyedian SS¹ ; Mohammadnejad A^{4, 5} ; Nabavizadeh B¹ ; Razavi AE^{4, 5} ; Esmaeilipour R¹ Show Affiliations
Source: Regenerative Engineering and Translational Medicine Published:2023

Abstract

Purpose: We focused on the composition and architecture of the prostate extracellular matrix (ECM) and interactions with its cellular constituents. We also discussed the role of ECM remodeling on cellular behaviors in vivo. Methods: Nine natural, BPH, and malignant human prostate tissues were decellularized using a modified technique. Then, the scaffolds were implanted adjacent to the prostate in nine male GFP-positive rats which were randomly divided into group A (n = 3, natural), group B (n = 3, BPH), and group C (n = 3, malignant tissue). Biopsies were taken after six months of implantation to assess the quality of recellularization by histological evaluations. We also evaluated the impact of malignant and BPH prostatic ECM on cell proliferation, differentiation, and expression of ECM components in follow-up. Results: Cell removal with preservation of ECM structure was confirmed in all decellularized prostates. Histological examinations after the decellularization process illustrated down-regulated expression of laminin and vimentin in normal, BPH, and malignant tissues. Furthermore, malignant samples revealed simply lower levels in type IV Collagen content of the ECM. All of the implanted samples also contained an abundance of newly formed vessels suggestive of prominent angiogenesis. Immunostaining of all scaffolds after implantation was negative for AMACR marker revealing the absence of cancerous cells in the recellularized tissues in follow-up. The samples in group C demonstrated the highest decrease in the ECM content after recellularization. Conclusion: The outcomes could bring us one step closer to understanding the complex dynamics of ECM–cell interactions in prostate adenocarcinoma. We concluded that the expression of some markers may change in malignant human prostatic tissues after the decellularization process. Lay summary: Previously, we used recellularization of testicular feminization testis in C57bl6 as a natural bio-reactor for the creation of cellularized seminiferous tubules. In this study, we try to evaluate the composition and architecture of the prostate ECM and its interactions with its cellular constituents. We also aim to assess the role of ECM remodeling on cellular behaviors in vivo. Future works: We will emphasize on assessing in vitro and in vivo characteristics of bio-scaffolds from diverse benign and malignant tissues. We will also examine the role of ECM behavior on the development of prostate cancer in our long-term follow-ups. © 2023, The Author(s), under exclusive licence to The Regenerative Engineering Society.