Case Report
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jul 26, 2021; 13(7): 944-970
Published online Jul 26, 2021. doi: 10.4252/wjsc.v13.i7.944
First immunohistochemical evidence of human tendon repair following stem cell injection: A case report and review of literature
Eckhard Alt, Ralf Rothoerl, Matthias Hoppert, Hans-Georg Frank, Tobias Wuerfel, Christopher Alt, Christoph Schmitz
Eckhard Alt, Chairman of the Board, Isarklinikum Munich, Munich 80331, Germany
Ralf Rothoerl, Department of Spine Surgery, Isarklinikum Munich, Munich 80331, Germany
Matthias Hoppert, Department for Orthopedics and Trauma Surgery, Isarklinikum Munich, Munich 80331, Germany
Hans-Georg Frank, Tobias Wuerfel, Christoph Schmitz, Chair of Neuroanatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Munich 80336, Germany
Christopher Alt, Director of Science and Research, InGeneron GmbH, Munich 80331, Germany
Author contributions: Alt EU, Rothoerl R, Hoppert M, Frank HG, Wuerfel T, Alt C and Schmitz C designed the report; Rothoerl R and Hoppert M performed treatment and collected the biopsy; Alt EU, Frank HG, Alt C and Schmitz C collected the patient’s clinical data; Alt EU, Frank HG, Wuerfel T, Alt C and Schmitz C analyzed the data and wrote the paper.
Informed consent statement: Consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: Alt EU is Executive Chair of InGeneron, Inc. (Houston, TX) and Chairman of the Board of Isar Klinikum (Munich, Germany). Alt C is Director of Science and Research of InGeneron GmbH (Munich, Germany) and of SciCoTec (Grünwald, Germany), the principal shareholder of InGeneron, Inc., which owns InGeneron GmbH (Munich, Germany). Schmitz C served as consultant to SciCoTec and the Alliance of Cardiovascular Researchers, and is Advisory Medical Director of InGeneron, Inc.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
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: Eckhard Alt, MD, PhD, Professor, Chairman of the Board, Isarklinikum Munich, Sonnenstr. 24-26, Munich 80331, Germany. e.alt@biomed-science.com
Received: January 29, 2021
Peer-review started: January 29, 2021
First decision: February 28, 2021
Revised: April 29, 2021
Accepted: June 25, 2021
Article in press: June 25, 2021
Published online: July 26, 2021
Processing time: 175 Days and 2.3 Hours
Abstract
BACKGROUND

Current clinical treatment options for symptomatic, partial-thickness rotator cuff tear (sPTRCT) offer only limited potential for true tissue healing and improvement of clinical results. In animal models, injections of adult stem cells isolated from adipose tissue into tendon injuries evidenced histological regeneration of tendon tissue. However, it is unclear whether such beneficial effects could also be observed in a human tendon treated with fresh, uncultured, autologous, adipose derived regenerative cells (UA-ADRCs). A specific challenge in this regard is that UA-ADRCs cannot be labeled and, thus, not unequivocally identified in the host tissue. Therefore, histological regeneration of injured human tendons after injection of UA-ADRCs must be assessed using comprehensive, immunohistochemical and microscopic analysis of biopsies taken from the treated tendon a few weeks after injection of UA-ADRCs.

CASE SUMMARY

A 66-year-old patient suffered from sPTRCT affecting the right supraspinatus and infraspinatus tendon, caused by a bicycle accident. On day 18 post injury [day 16 post magnetic resonance imaging (MRI) examination] approximately 100 g of abdominal adipose tissue was harvested by liposuction, from which approximately 75 × 106 UA-ADRCs were isolated within 2 h. Then, UA-ADRCs were injected (controlled by biplanar X-ray imaging) adjacent to the injured supraspinatus tendon immediately after isolation. Despite fast clinical recovery, a follow-up MRI examination 2.5 mo post treatment indicated the need for open revision of the injured infraspinatus tendon, which had not been treated with UA-ADRCs. During this operation, a biopsy was taken from the supraspinatus tendon at the position of the injury. A comprehensive, immunohistochemical and microscopic analysis of the biopsy (comprising 13 antibodies) was indicative of newly formed tendon tissue.

CONCLUSION

Injection of UA-ADRCs can result in regeneration of injured human tendons by formation of new tendon tissue.

Keywords: Stem cells; Partial-thickness rotator cuff tear; Tendon regeneration; Adipose derived regenerative cells; Cell-based therapy at point of care; Case report

Core Tip: Current treatment options for partial-thickness rotator cuff tear do not offer the potential to form new tendon tissue. The results of this study suggest, for the first time, that treating an injured human supraspinatus tendon with fresh, uncultured, autologous, adipose derived regenerative cells prepared at the point of care enables regenerative healing of an injured tendon, as evidenced by comprehensive immunohistochemical analysis of a biopsy taken from the patient’s tendon 2.5 mo post treatment. Regenerative healing without scar formation has previously been attributed only to fetal tendon development.