Copyright
©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Effects of immune cells on mesenchymal stem cells during fracture healing
Sabrina Ehnert, Borna Relja, Katharina Schmidt-Bleek, Verena Fischer, Anita Ignatius, Caren Linnemann, Helen Rinderknecht, Markus Huber-Lang, Miriam Kalbitz, Tina Histing, Andreas K Nussler
Sabrina Ehnert, Caren Linnemann, Helen Rinderknecht, Tina Histing, Andreas K Nussler, Siegfried Weller Research Institute at the BG Trauma Center Tübingen, Department of Trauma and Reconstructive Surgery, University of Tübingen, Tübingen 72076, Germany
Borna Relja, Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke University, Magdeburg 39120, Germany
Katharina Schmidt-Bleek, Julius Wolff Institute and Berlin Institute of Health Center of Regenerative Therapies, Charité - University Medicine Berlin, Berlin 13353, Germany
Verena Fischer, Anita Ignatius, Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, Ulm 89091, Germany
Markus Huber-Lang, Institute for Clinical and Experimental Trauma-Immunology (ITI), University Hospital Ulm, Ulm 89091, Germany
Miriam Kalbitz, Department of Trauma and Orthopedic Surgery, University Hospital Erlangen Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen 91054, Germany
Author contributions: Each author performed a literature research for a specific section of the review article; Each author wrote a section of the review article; Ehnert S and Nussler AK compiled the individual sections; Ehnert S produced the graphics; all authors reviewed and edited the compiled manuscript.
Supported by German Research Foundation (DFG) focusing on “Interplay between mononuclear and osteogenic cells during fracture healing in type 2 diabetics“, No. EH 471/2 (to Ehnert S); German Research Foundation within the context of the Collaborative Research Center (CRC) 1149 “Danger Response, Disturbance Factors and Regenerative Potential after Acute Trauma”, No. 251293561, C01 (to Ignatius A and Fischer V); DFG in context of the CRC 1149, No. 251293561, A01 and No. 251293561 Z02 (to Huber-Lang M); and DFG in the context of the CRC 1149, No. 251293561, C07 (to Kalbitz M).
Conflict-of-interest statement: The authors declare no conflict of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Andreas K Nussler, PhD, Academic Research, Director, Pharmacist, Professor, Senior Scientist, Siegfried Weller Research Institute at the BG Trauma Center Tübingen, Department of Trauma and Reconstructive Surgery, University of Tübingen, Schnarrenbergstr. 95, Tübingen 72076, Germany.
andreas.nuessler@med.uni-tuebingen.de
Received: February 28, 2021
Peer-review started: February 28, 2021
First decision: March 29, 2021
Revised: March 31, 2021
Accepted: September 3, 2021
Article in press: September 3, 2021
Published online: November 26, 2021
Processing time: 269 Days and 15.8 Hours
In vertebrates, bone is considered an osteoimmune system which encompasses functions of a locomotive organ, a mineral reservoir, a hormonal organ, a stem cell pool and a cradle for immune cells. This osteoimmune system is based on cooperatively acting bone and immune cells, cohabitating within the bone marrow. They are highly interdependent, a fact that is confounded by shared progenitors, mediators, and signaling pathways. Successful fracture healing requires the participation of all the precursors, immune and bone cells found in the osteoimmune system. Recent evidence demonstrated that changes of the immune cell composition and function may negatively influence bone healing. In this review, first the interplay between different immune cell types and osteoprogenitor cells will be elaborated more closely. The separate paragraphs focus on the specific cell types, starting with the cells of the innate immune response followed by cells of the adaptive immune response, and the complement system as mediator between them. Finally, a brief overview on the challenges of preclinical testing of immune-based therapeutic strategies to support fracture healing will be given.
Core Tip: There is substantial evidence that immune cells influence mesenchymal stem cells (MSCs) after trauma. Bone is considered as an osteoimmune system based on cooperatively acting bone and immune cells, cohabitating within the bone marrow. The subdivisions are highly interdependent, sharing progenitors, mediators, and signaling pathways. During fracture healing many different cell types categorized to the innate and adaptive immune system interact. MSCs with their manifold immunomodulatory and regenerative properties serve as progenitors for fibroblasts, chondrocytes and osteoblasts. The alterations in the immune response usually become apparent early in the healing process of a fracture. This opens new avenues for early interventions.
