Regenexx is a Research Based Stem Cell Procedure
The original Regenexx-C procedure was first used as part of an IRB supervised clinical trial from 2005-2007. During this time our medical practice invested hundreds of thousands of dollars in providing investigational care, with all patients receiving before and after research-grade MRI’s. For more information on how physicians innovate versus how FDA/drug companies discover new drugs, see this link. By late 2007, once the physicians were satisfied that the procedure was working and that the complications were less than existing surgical care, the clinic began treating patients. Since that time the clinic has published many medical research papers listed in the U.S. Library of Medicine (see this link for an incomplete list). Every patient treated by us is entered into a treatment registry and will be contacted at various time points regarding the outcome of the procedure, any complications, etc… As a result, we have extensive experience in what works and what doesn’t work. In addition, based on our published complications papers, our procedure produces significantly fewer complications than the more invasive surgical procedures it helps many patients avoid.
In addition to peer reviewed publications, we also publish our registry data online. See data on Regenexx-SD and the Regenexx-PL-Disc procedures. Pre-publication data and before/after MRI case studies can often be found on the Regenexx blog.
[Disclaimer: The Regenexx same day procedures (-SD, -AD, -SCP, -PL-Disc, etc...) are performed in the United States. The Regenexx-C cultured stem cell procedure is only offered through RegenexxCayman, which is an independently owned and operated medical services provider operating exclusively in the Cayman Islands and is not part of or affiliated with the Centeno-Schultz Clinic or any U.S. Regenexx Network provider. The Regenexx-C procedure licensed by RegenexxCayman is not approved by the U.S. FDA for use in the United States.]
Published Research:
A Case Series of Percutaneous Treatment of Non-Union Fractures with Autologous, Culture Expanded, Bone Marrow Derived, Mesenchymal Stem Cells and Platelet Lysate
Centeno CJ, Schultz JR, Cheever M, Freeman M, Robinson B, Faulkner S
–Journal of Bioengineering and Biomedical Science. 2011
Abstract
Background: Current treatment options for stable non-union fractures represent major clinical challenges, and are a major health issue. Fracture treatment can take many forms, usually requiring bone grafting and/or revisions of the fracture with open reduction and internal fixation (ORIF). Conservative care options such as bone morphogenic proteins and bone stimulators are also available. The purpose of this study was to determine if culture expanded, autologous MSC’s injected into non-union fractures under c-Arm fluoroscopy could represent an alternative treatment modality in recalcitrant fracture non-unions. This paper reports on the findings of 6 patients with fracture non-union treated with autologous MSC’s. Patients and methods: We evaluated 6 consecutive patients with chronic fracture non-unions. Patients consisted of 4 women and 2 men with treatment intervention at an average of 8.75 months post-fracture (range 4- 18 months, one patient fracture not included in calculation was >100 mo.). All treated patients received autologous, culture expanded, mesenchymal stem cells injected percutaneously via fluoroscopic guidance into the site of the fracture non-union. Fracture union was evaluated with the use of follow up high-resolution x-ray and/or CT imaging. Phenotype of the culture-expanded MSCs was evaluated and quantified by flow cytometry of surface antigens.Conclusion: The results of this study support the hypothesis that autologous MSC’s delivered via percutaneous re-implantation may be an alternative modality for the non-operative treatment of recalcitrant non-union fractures.
Safety and Complications Reporting Update on the Re-implantation of Culture-Expanded Mesenchymal Stem Cells using Autologous Platelet Lysate Technique.
Source
The Centeno-Schultz Clinic, Broomfield, Colorado, USA.
Abstract
Mesenchymal stem cells (MSCs) hold great promise as therapeutic agents in regenerative medicine. Numerous animal studies have documented the multipotency of MSCs, showing their capabilities for differentiating into orthopedic tissues such as muscle, bone, cartilage, and tendon. However, the safety of culture expanded MSC’s for human use has only just begun to be reported. Methods: Between 2006 and 2010, two groups of patients were treated for various orthopedic conditions with culture-expanded, autologous, bone marrow-derived MSCs (group 1: n=50; group 2: n=290-one patient in both groups). Cells were cultured in monolayer culture flasks using an autologous platelet lysate technique and re-injected into peripheral joints or into intervertebral discs with use of c-arm fluoroscopy. While both groups had prospective surveillance for complications, Group 1 additionally underwent 3.0T MRI tracking of the re-implant sites. Results: The mean age of patients treated was 53 +/- 13.85 years; 214 were males and 125 females with mean follow-up time from any procedure being 435 days +/- 261 days. Number of contacts initiated based on time from first procedure was 482 at 3 months, 433 at 6 months, 316 contacts at 12 months, 110 contacts at 24 months, and 22 contacts at 36 months. For Group 1, 50 patients underwent 210 MRI surveillance procedures at 3 months, 6 months, 1 year and 2 years which failed to demonstrate any tumor formation at the re-implant sites. Formal disease surveillance for adverse events based on HHS criteria documented significantly less morbidity than is commonly reported for more invasive surgical procedures, all of which were either self-limited or were remedied with therapeutic measures. Two patients were diagnosed with cancer out of 339 patients treated since study inception; however, this was almost certainly unrelated to the MSC therapy and the neoplasm rate in similar to that seen in the U.S. Caucasian population. Knee outcome data was collected on a subset of patients. Here, >75% improvement was reported in 41.4% while decreasing the improvement threshold to >50% improvement, 63.2% reported an improvement. At an average reporting time of 11.3 months from first procedure average reported relief in the knee sample equaled 53.1% (n=133 reporting). Conclusions: Using both intensive high field MRI tracking and complications surveillance in 339 patients, no neoplastic complications were detected at any stem cell re-implantation site. These findings are consistent with our prior publication and other published reports that also show no evidence of malignant transformation in vivo, following implantation of MSCs for orthopedic use.
- PMID:
- 22023622
- [PubMed - as supplied by publisher]
–Journal of American Physicians and Surgeons Volume 16 Number 2 Summer 201
The Use of Mesenchymal Stem Cells in Orthopedics:Review of the Literature, Current Research,and Regulatory Landscape
Christopher J. Centeno, M.D., Stephen Faulkner, B.A
Abstract:
Mesenchymal stem cells (MSCs) show promising clinicalpotential as multi-potent therapeutic agents in regenerativemedicine, including a number of orthopedic applications. Acomprehensive review of the medical literature regarding thepre-clinical and early clinical use ofMSCs demonstrates that theyare likely to be effective cellular repair agents for cartilage andjoint injuries.Cultured MSCs were injected into the knee joints of 153patients with moderate to severe osteoarthritis (OA) of the knee.The study included 24 untreated patient candidates who wererecruited as controls. At a mean follow-up of 11.3 months, kneepatients reported mean pain relief as +53.1% (n=133), and -5.0%relief was found in the untreated control (n=25 at 12.0 monthspost-op) ( <.001 for control vs. knee comparison). Significantdecreases were seen in four out of five of the Visual Analog Scale(VAS) score metrics and in most functional metrics in the kneegroup.There were no serious complications reported.MSCs may reduce the need for joint replacement in kneeosteoarthritis. Despite the great potential of the use ofautologous MSCs as the practice of medicine, the Food and DrugAdministration (FDA) has attempted to regulate MSCs as a drug.This policy is inconsistent with its policy on other mattersincluding tissue re-implantation and in vitro fertilization, and willdelay the development ofthis type oftherapy
Safety and complications reporting on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique.
Centeno CJ, Schultz JR, Cheever M, Robinson B, Freeman M, Marasco W.
Centeno-Schultz Clinic, Broomfield, Colorado, USA. [email protected]
–Curr Stem Cell Res Ther. 2010 Mar;5(1):81-93.
Abstract
ABSTRUCT: Mesenchymal stem cells (MSCs) hold great promise as therapeutic agents in regenerative medicine. Numerous animal studies have documented the multipotency of MSCs, showing their capabilities for differentiating into orthopedic tissues such as muscle, bone, cartilage, and tendon. However, the complication rate for autologous MSC therapy is only now beginning to be reported. METHODS: Between 2005 and 2009, two groups of patients were treated for various orthopedic conditions with culture-expanded, autologous, bone marrow-derived MSCs (group 1: n=45; group 2: n=182). Cells were cultured in monolayer culture flasks using an autologous platelet lysate technique and re-injected into peripheral joints (n=213) or into intervertebral discs (n=13) with use of c-arm fluoroscopy. While both groups had prospective surveillance for complications, Group 1 additionally underwent 3.0T MRI tracking of the re-implant sites. RESULTS: Mean follow-up from the time of the re-implant procedure was 10.6 +/- 7.3 months. Serial MRI’s at 3 months, 6 months, 1 year and 2 years failed to demonstrate any tumor formation at the re-implant sites. Formal disease surveillance for adverse events based on HHS criteria documented 7 cases of probable procedure-related complications (thought to be associated with the re-implant procedure itself) and three cases of possible stem cell complications, all of which were either self-limited or were remedied with simple therapeutic measures. One patient was diagnosed with cancer; however, this was almost certainly unrelated to the MSC therapy. CONCLUSIONS: Using both high field MRI tracking and general surveillance in 227 patients, no neoplastic complications were detected at any stem cell re-implantation site. These findings are consistent with other reports that also show no evidence of malignant transformation in vivo, following implantation of MSCs that were expanded in vitro for limited periods.
PMID: 19951252 [PubMed - in process]
Osteoblastic differentiation of human and equine adult bone marrow-derived mesenchymal stem cells when BMP-2 or BMP-7 homodimer genetic modification is compared to BMP-2/7 heterodimer genetic modification in the presence and absence of dexamethasone.
Carpenter RS, Goodrich LR, Frisbie DD, Kisiday JD, Carbone B, McIlwraith CW, Centeno CJ, Hidaka C.
Orthopaedic Research Center, Colorado State University, Fort Collins, Colorado 80523.
–J Orthop Res. 2010 Mar 22. [Epub ahead of print]
Abstract
Bone marrow-derived mesenchymal stem cells (BMDMSCs) have been targeted for use in enhancement of bone healing; and their osteogenic potential may be further augmented by genes encoding bone morphogenetic proteins (BMP’s). The purpose of this study was to compare the effect of genetic modification of human and equine BMDMSCs with BMP-2 or -7 or BMP-2 and -7 on their osteoblastogenic differentiation in the presence or absence of dexamethasone. The BMDMSCs were harvested from the iliac crest of three human donors and tuber coxae of three equine donors. Monolayer cells were genetically modified using adenovirus vectors encoding BMP-2, -7 or both and cultured in the presence or absence of dexamethasone. Expression of BMPs was confirmed by enzyme linked immunosorbent assay (ELISA). To evaluate osteoblastic differentiation, cellular morphology was assessed every other day and expression and secretion of alkaline phosphatase (ALP), as well as expression levels of osteonectin (OSTN), osteocalcin (OCN), and runt-related transcription factor-2 (Runx2) were measured for up to 14 days. Human and equine BMDMSCs showed a capacity for osteogenic differentiation regardless of genetic modification or dexamethasone supplementation. Dexamethasone supplementation was more important for osteoblastogenic differentiation of equine BMDMSCs than human BMDMSCs. Genetic modification of BMDMSCs increased ALP secretion with AdBMP-2 homodimer having the greatest effect in both human and equine cells compared to AdBMP 7 or AdBMP 2/7. BMP protein elution rates reached their maximal concentration between day 4 and 8 and remained relatively stable thereafter, suggesting that genetically modified BMDMSCs could be useful for cell-based delivery of BMPs to a site of bone formation. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
PMID: 20309952 [PubMed - as supplied by publisher]
Regeneration of meniscus cartilage in a knee treated with percutaneously implanted autologous mesenchymal stem cells.
Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D.
Regenerative Sciences Inc, Centeno-Schultz Clinic, Westminster, CO 80020, USA.
–Med Hypotheses. 2008 Dec;71(6):900-8. Epub 2008 Sep 10.
Abstract
Mesenchymal stem cells are pluripotent cells found in multiple human tissues including bone marrow, synovial tissues, and adipose tissues. They have been shown to differentiate into bone, cartilage, muscle, and adipose tissue and represent a possible promising new therapy in regenerative medicine. Because of their multi-potent capabilities, mesenchymal stem cell (MSC) lineages have been used successfully in animal models to regenerate articular cartilage and in human models to regenerate bone. The regeneration of articular cartilage via percutaneous introduction of mesenchymal stem cells (MSC’s) is a topic of significant scientific and therapeutic interest. Current treatment for cartilage damage in osteoarthritis focuses on surgical interventions such as arthroscopic debridement, microfracture, and cartilage grafting/transplant. These procedures have proven to be less effective than hoped, are invasive, and often entail a prolonged recovery time. We hypothesize that autologous mesenchymal stem cells can be harvested from the iliac crest, expanded using the patient’s own growth factors from platelet lysate, then successfully implanted to increase cartilage volume in an adult human knee. We present a review highlighting the developments in cellular and regenerative medicine in the arena mesenchymal stem cell therapy, as well as a case of successful harvest, expansion, and transplant of autologous mesenchymal stem cells into an adult human knee that resulted in an increase in meniscal cartilage volume.
PMID: 18786777 [PubMed - indexed for MEDLINE]
Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells.
Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D.
Regenerative Sciences Inc (RSI), Centeno-Schultz Clinic, Westminster, CO 80020, USA.
–Pain Physician. 2008 May-Jun;11(3):343-53.
Abstract
BACKGROUND: The ability to repair tissue via percutaneous means may allow interventional pain physicians to manage a wide variety of diseases including peripheral joint injuries and osteoarthritis. This review will highlight the developments in cellular medicine that may soon permit interventional pain management physicians to treat a much wider variety of clinical conditions and highlight an interventional case study using these technologies OBJECTIVE: To determine if isolated and expanded human autologous mesenchymal stem cells could effectively regenerate cartilage and meniscal tissue when percutaneously injected into knees. DESIGN: Case Study SETTING: Private Interventional Pain Management practice. METHODS: An IRB approved study with a consenting volunteer in which mesenchymal stem cells were isolated and cultured ex-vivo from bone marrow aspiration of the iliac crest. The mesenchymal stem cells were then percutaneously injected into the subject’s knee with MRI proven degenerative joint disease. Pre- and post-treatment subjective visual analog pain scores, physical therapy assessments, and MRIs measured clinical and radiographic changes. RESULTS: At 24 weeks post-injection, the patient had statistically significant cartilage and meniscus growth on MRI, as well as increased range of motion and decreased modified VAS pain scores. CONCLUSION: The described process of autologous mesenchymal stem cell culture and percutaneous injection into a knee with symptomatic and radiographic degenerative joint disease resulted in significant cartilage growth, decreased pain and increased joint mobility in this patient. This has significant future implications for minimally invasive treatment of osteoarthritis and meniscal injury.
PMID: 18523506 [PubMed - indexed for MEDLINE]Free Article
Partial regeneration of the human hip via autologous bone marrow nucleated cell transfer: A case study.
Centeno CJ, Kisiday J, Freeman M, Schultz JR.
The Centeno-Schultz Clinic, 11080 Circle Point Road, Building 2, Suite 140, Westminster, CO 80020, USA. [email protected]
–Pain Physician. 2006 Jul;9(3):253-6.
Abstract
HISTORY: This is a case report of a 64-year-old white male with a 20 year history of unilateral hip pain that had become debilitating over the last several years. On intake, Harris hip score was rated as: Pain subscale = 10, Function subscale = 32, Deformity subscale = 4, Motions subscale = 4.775 with a total score of 50.8 out of 100. MRI of the affected hip showed severe degeneration with spurring, decrease in joint space, and several large subchondral cysts. The patient had been evaluated by an orthopedic surgeon and told he was a candidate for bipolar hip replacement. METHOD: Two autologous nucleated cell collections were performed from bone marrow with subsequent isolation and transfers into the intra-articular hip using a hyaluronic acid and thrombin activated platelet rich plasma scaffold. Marrow samples were processed by centrifugation and lysis techniques to isolate nucleated cells. CONCLUSION: This report describes partial by articular surface regeneration 8 weeks after intraarticular bone marrow transfer. Post-op 3.0T FGRE MRI showed neocortex formation when compared to immediate pre-op MRI and objective improvements were noted that coincided with subjective reports of improvement.
PMID: 16886034 [PubMed - indexed for MEDLINE]Free Article
