Citation: Roi, A.; Roi, C.; Negrut , iu, M.L.; Rusu, L.C.; Rivis , , M. Mesenchymal Stem Cells Derived from Human Periapical Cysts and Their Implications in Regenerative Medicine. Biomedicines 2023, 11, 2436. https://doi.org/10.3390/ biomedicines11092436 Academic Editors: Takayoshi Yamaza and Issei Saitoh Received: 3 August 2023 Revised: 27 August 2023 Accepted: 28 August 2023 Published: 31 August 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). biomedicines Review Mesenchymal Stem Cells Derived from Human Periapical Cysts and Their Implications in Regenerative Medicine Alexandra Roi 1,2 , Ciprian Roi 2,3, * , Meda Lavinia Negrut , iu 4,5 , Laura Cristina Rusu 1,2 and Mircea Rivis , 2,3 1 Department of Oral Pathology, “Victor Babes , ” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timis , oara, Romania; alexandra.moga@umft.ro (A.R.); laura.rusu@umft.ro (L.C.R.) 2 Multidisciplinary Center for Research, Evaluation, Diagnosis and Therapies in Oral Medicine, “Victor Babes , ” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timis , oara, Romania; rivis.mircea@umft.ro 3 Department of Anesthesiology and Oral Surgery, “Victor Babes , ” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timis , oara, Romania 4 Department of Prostheses Technology and Dental Materials, Faculty of Dental Medicine, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Sq. No. 2, 300041 Timis , oara, Romania; negrutiu.meda@umft.ro 5 Research Center in Dental Medicine Using Conventional and Alternative Technologies, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Sq. No. 2, 300041 Timis , oara, Romania * Correspondence: ciprian.roi@umft.ro Abstract: Mesenchymal stem cells currently play an important role in the tissue engineering field in developing new regenerative approaches. The oral cavity is a rich source of mesenchymal stem cells, and introducing the use of dental stem cells, characterized by a multilineage differentiation potential, immunomodulatory activity and repair capacity, offers a good perspective for clinical dentistry. Human periapical cyst mesenchymal stem cells (hPCy-MSCs) represent a new category of dental stem cells, being collected from pathological tissue and exhibiting MSCs-like properties. As studies have described, these new identified cells possess the same characteristics as those described in MSCs, exhibiting plasticity, a high proliferation rate and the potential to differentiate into osteogenic, adipogenic and neural lineages. Reusing the biological tissue that is considered pathologic offers a new perspective for the development of further clinical applications. The identification and characterization of MSCs in the human periapical cysts allows for a better understanding of the molecular interactions, the potential healing capacity and the mechanisms of inducing the local osteogenic process, integrated in the microenvironment. Although their involvement in regenerative medicine research is recent, they exhibit important properties that refer them for the development of clinical applications in dentistry. Keywords: dental mesenchymal stem cells; hPCy-MSCs; tissue engineering; regenerative dentistry 1. Introduction Mesenchymal stem cells (MSCs) represent the future in regenerative medicine, offering wide perspectives for clinical applications. One of their main properties is the ability to differentiate into various types of cells, as well as their capacity to self-renew, in order to provide a regenerative action. Their initial isolation was performed from the human bone marrow (BMMSCs), re- quiring invasive surgical procedures and limiting the final number of cells [1]. Currently, alternative approaches for eligible new sources of MSCs are those isolated from blood, adi- pose tissue, umbilical cord tissue, placenta, muscles, heart tissue and the dental pulp [2–4]. Biomedicines 2023, 11, 2436. https://doi.org/10.3390/biomedicines11092436 https://www.mdpi.com/journal/biomedicines