Secondary Logo

Journal Logo

Reply to the Letter to the Editor

Stem Cells Combined With Platelet-rich Plasma Effectively Treat Corticosteroid-induced Osteonecrosis of the Hip

A Prospective Study

Houdek, Matthew T. MD; Wyles, Cody C. MD; Collins, Mark S. MD; Howe, Benjamin M. MD; Terzic, Andre MD, PhD; Behfar, Atta MD, PhD; Sierra, Rafael J. MD

Clinical Orthopaedics and Related Research®: May 2018 - Volume 476 - Issue 5 - p 1129–1130
doi: 10.1007/s11999.0000000000000284
Other Features

M. T. Houdek, C. C. Wyles, R. J. Sierra, Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA

M. S. Collins, B. M. Howe, Department of Radiology, Mayo Clinic, Rochester, MN, USA

A. Terzic, A. Behfar, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA

R. J. Sierra MD, Mayo Clinic, Department of Orthopedic Surgery, 200 First Street SW, Rochester, MN 55905, USA, Email:

(RE: Houdek MT, Wyles CC, Collins MS, Howe BM, Terzic A, Behfar A, Sierra RJ. Stem Cells Combined With Platelet-rich Plasma Effectively Treat Corticosteroid-induced Osteonecrosis of the Hip: A Prospective Study. Clin Orthop Relat Res. 2018;476:388-397).

The authors certify that neither they, nor any members of their immediate families, have any commercial associations (such as consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article.

All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.

The opinions expressed are those of the writers, and do not reflect the opinion or policy of CORR® or The Association of Bone and Joint Surgeons®.

Received February 28, 2018

Accepted March 06, 2018

To the Editor,

We thank Dr. Piuzzi for his thoughtful critique of our study. He is correct in noting that the nomenclature for the definition of mesenchymal stem cells (MSCs) needs to be standardized, and although not explicitly stated in the methods section of the study that Dr. Piuzzi commented on [5], our previous studies, which describe our technique for isolating MSCs [5, 6, 10], meet the criteria proposed by the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy to define human mesenchymal stromal/stem cells.

Dr. Piuzzi is correct in pointing out that the bone marrow concentrate (BMC) isolated in the aspirate contains several different cell types and only a small percentage are true MSCs. However, we have isolated and characterized this subpopulation of cells from BMC in our previous studies [5, 6, 10], and we are currently in the process of performing a prospective randomized clinical trial ( NCT03269409) to build upon our knowledge of the unaltered BMC at the time of surgery. Indeed, we will soon be able to determine exactly how much of every cell type is derived during each core decompression including MSCs, vascular progenitors, macrophages, and lymphocytes. Likewise, we are also harvesting adipose-derived MSCs to determine if they will have a greater impact on healing, as our in vitro study has suggested [10].

Dr. Piuzzi notes that many studies have focused on MSCs [1, 2, 4-10], and we agree that other cell types may be important as well, which is why our current clinical trial is exploring them. Still, MSCs are the focus because the evidence suggests that they are the key regenerative cell population in adjuvant biologic therapies such as BMC [3].

We thank Dr. Piuzzi for his contributions to the clinical field of regenerative orthopaedic surgery. We agree that high-quality studies, with quantitative methods for cell harvesting, processing, characterization, and delivery, are important. We would like to add that studies examining clinical and structural outcomes, while still needed, are a primary focus of our currently enrolling prospective randomized clinical trial.

Back to Top | Article Outline


1. Gangji V, Hauzeur JP. Treating osteonecrosis with autologous bone marrow cells. Skeletal Radiol. 2010;39:209–211.
2. Gangji V, Hauzeur JP, Matos C, De Maertelaer V, Toungouz M, Lambermont M. Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells. A pilot study. J Bone Joint Surg Am. 2004;86:1153–1160.
3. Grayson WL, Bunnell BA, Martin E, Frazier T, Hung BP, Gimble JM. Stromal cells and stem cells in clinical bone regeneration. Nat Rev Endocrinol. 2015;11:140–150.
4. Hernigou P, Beaujean F. Treatment of osteonecrosis with autologous bone marrow grafting. Clin Orthop Relat Res. 2002;405:14–23.
5. Houdek MT, Wyles CC, Collins MS, Howe BM, Terzic A, Behfar A, Sierra RJ. Stem cells combined with platelet-rich plasma effectively treat corticosteroid-induced osteonecrosis of the hip: A prospective study. Clin Orthop Relat Res. 2018;476:388–397.
6. Houdek MT, Wyles CC, Packard BD, Terzic A, Behfar A, Sierra RJ. Decreased osteogenic activity of mesenchymal stem cells in patients with corticosteroid-induced osteonecrosis of the femoral head. J Arthroplasty. 2016;31:893–898.
7. Lim YW, Kim YS, Lee JW, Kwon SY. Stem cell implantation for osteonecrosis of the femoral head. Exp Mol Med. 2013;45:e61.
8. Martin JR, Houdek MT, Sierra RJ. Use of concentrated bone marrow aspirate and platelet rich plasma during minimally invasive decompression of the femoral head in the treatment of osteonecrosis. Croat Med J. 2013;54:219–224.
9. Sen RK, Tripathy SK, Aggarwal S, Marwaha N, Sharma RR, Khandelwal N. Early results of core decompression and autologous bone marrow mononuclear cells instillation in femoral head osteonecrosis: a randomized control study. J Arthroplasty. 2012;27:679–686.
10. Wyles CC, Houdek MT, Crespo-Diaz RJ, Norambuena GA, Stalboerger PG, Terzic A, Behfar A, Sierra RJ. Adipose-derived mesenchymal stem cells are phenotypically superior for regeneration in the setting of osteonecrosis of the femoral head. Clin Orthop Relat Res. 2015;473:3080–3090.
© 2018 Lippincott Williams & Wilkins LWW