Safety and complications reporting update on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique.
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, 2, and 3 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.
The Centeno-Schultz Clinic, Broomfield, Colorado, USA. centenooffice@centenoschultzclinic.com
Christopher J
CJ
Centeno
John R
JR
Schultz
Michelle
M
Cheever
Michael
M
Freeman
Stephen
S
Faulkner
Brent
B
Robinson
Ronald
R
Hanson
D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology; D018929:Cell Culture Techniques; D004341:Drug Evaluation; D005260:Female; D005471:Fluoroscopy / Q000379:methods; D005500:Follow-Up Studies; D006801:Humans; D007719:Knee Joint / Q000378:metabolism* / Q000601:surgery; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008875:Middle Aged; D019637:Orthopedic Procedures; D011446:Prospective Studies; D044968:Regenerative Medicine; D012092:Replantation / Q000009:adverse effects / Q000379:methods*; D011795:Surveys and Questionnaires; D014182:Transplantation, Autologous / Q000379:methods*; D016896:Treatment Outcome