This post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.
One of the key changes leading to intervertebral disc degeneration is the loss of complex proteoglycans in the nucleus pulposus (NP), which leads to a loss of water avidity, physiologic dysfunction, NP tissue rigidity, and disruption of surrounding disc tissues. In humans, these changes can begin as early as the second decade of life. One of the difficulties in developing cellular therapies to address these changes is creating a hydrogel that can support effective delivery of mesenchymal stem cells (MSCs).
University of Pennsylvania researchers chemically induced degeneration in lumbar discs in adult male goats. After 12 weeks, some of the degenerating discs were injected with either a hydrogel alone (n=9 discs) or hydrogel with 10 million mesenchymal stem cells per ml (n=10 discs). The remaining discs received neither injection. Two weeks later, researchers analyzed disc height, hydrogel distribution, and MSC localization using green fluorescent protein (GFP) immunostaining.
After 12 weeks of disc degeneration, disc height was approximately 66% of pre-intervention levels. After 2 weeks of the treatment phase, researchers found an insignificant increase in height in the hydrogel-alone discs, and a significant 7.6% height increase in the hydrogel-with-MSCs discs. Imaging revealed that the majority of hydrogel was located in the NPs of the treated discs.
Treated discs exhibited improved overall histological grade compared to untreated discs, but the improvement was significant only in discs treated with hydrogel + MSCs. The fact that GFP-positive MSCs were identified both in the hydrogel itself and in the surrounding NP tissue suggests that MSCs migrated beyond the injection site.
The question remains whether we can similarly improve physiology in the wide spectrum of degenerative disc disease experienced by humans. Let’s hope that future investigations yield positive findings.
Under one name or another, The Journal of Bone & Joint Surgery has published quality orthopaedic content spanning three centuries. In 1919, our publication was called the Journal of Orthopaedic Surgery, and the first volume of that journal was Volume 1 of what we know today as JBJS.
Thus, the 24 issues we turn out in 2018 will constitute our 100th volume. To help celebrate this milestone, throughout the year we will be spotlighting 100 of the most influential JBJS articles on OrthoBuzz, making the original content openly accessible for a limited time.
Unlike the scientific rigor of Journal content, the selection of this list was not entirely scientific. About half we picked from “JBJS Classics,” which were chosen previously by current and past JBJS Editors-in-Chief and Deputy Editors. We also selected JBJS articles that have been cited more than 1,000 times in other publications, according to Google Scholar search results. Finally, we considered “activity” on the Web of Science and The Journal’s websites.
We hope you enjoy and benefit from reading these groundbreaking articles from JBJS, as we mark our 100th volume. Here are two more:
Displaced Proximal Humeral Fractures: Classification and Evaluation
C Neer: JBJS, 1970 September; 52 (6): 1077
Complex distal humeral fractures have long challenged orthopaedic surgeons and their patients. Often the first step in fracture-management decision-making is classification, and in this 1970 study, Dr. Neer proposed a 6-group classification based on the presence or absence of displacement of one or more of the four major proximal segments. Since then, this classification has been variably adapted by multiple authors, but its usefulness remains intact.
The Effect of Implants Loaded with Autologous Mesenchymal Stem Cells on the Healing of Canine Segmental Bone Defects
S F Bruder, K H Kraus, V M Goldberg, S Kadiyala: JBJS, 1998 July; 80 (7): 985
Research into mesenchymal stem cells (MSCs) to augment healing of tendons, chondral and bone defects, and other connective tissues has taken off since these authors used autologous MSCs to help heal 21-mm segmental femoral defects. Radiographic union occurred rapidly at the interface between host bone and porous ceramic cylinders loaded with MSCs, and a large collar of bone had formed around the cell-loaded implants after 16 weeks.
The article “Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial menisectomy” is an interesting report of a randomized, double-blind, controlled study carried out over a 2-year period following subtotal medial menisectomy.
While the positive impact of mesenchymal stem cells (MSCs) on both the meniscus and articular cartilage has been demonstrated in animal models, this study looks at the potentially beneficial effects in humans after partial menisectomy. MSC injection in this setting resulted in no apparent complication secondary to these injections. Pain in patients with osteoarthritis was also improved over 2 years compared to those patients treated only with hyaluronate injection. Most intriguing, though, was that in 24% of patients with lower dose MSC and in 6% with higher dose MSC, there was an increase in meniscal volume on MRI by > 15%. None in the control group showed any volume change.
With the large number of meniscal injuries treated surgically in all age groups, MSC injection following partial menisectomy may prove to be a safe method to decrease osteoarthritic pain and potentially increase the volume of the remaining meniscus.