Autologous bone marrow stem cell intralesional transplantation repairing bisphosphonate related osteonecrosis of the jaw.

PURPOSE: Bisphosphonate - related osteonecrosis of the JAW (BRONJ) is a well known side effect of bisphosphonate therapies in oncologic and non oncologic patients. Since to date no definitive consensus has been reached on the treatment of BRONJ, novel strategies for the prevention, risk reduction and treatment need to be developed. We report a 75 year old woman with stage 3 BRONJ secondary to alendronate and pamidronate treatment of osteoporosis. The patient was unresponsive to recommended treatment of the disease, and her BRONJ was worsening. Since bone marrow stem cells are know as being multipotent and exhibit the potential for differentiation into different cells/tissue lineages, including cartilage, bone and other tissue, we performed autologous bone marrow stem cell transplantation into the BRONJ lesion of the patient. METHODS: Under local anesthesia a volume of 75 ml of bone marrow were harvested from the posterior superior iliac crest by aspiration into heparinized siringes. The cell suspension was concentrated, using Ficoll - Hypaque® centrifugation procedures, in a final volume of 6 ml. Before the injection of stem cells into the osteonecrosis, the patient underwent surgical toilet, local anesthesia was done and spongostan was applied as a carrier of stem cells suspension in the bone cavity, then 4 ml of stem cells suspension and 1 ml of patient's activated platelet-rich plasma were injected in the lesion of BRONJ. RESULTS: A week later the residual spongostan was removed and two weeks later resolution of symptoms was obtained. Then the lesion improved with progressive superficialization of the mucosal layer and CT scan, performed 15 months later, shows improvement also of bone via concentric ossification: so complete healing of BRONJ (stage 0) was obtained in our patient, and 30 months later the patient is well and without signs of BRONJ. CONCLUSION: To our knowledge this is the first case of BRONJ successfully treated with autologous stem cells transplantation with a complete response.

Bone marrow cell transplantation improves cardiac, autonomic, and functional indexes in acute anterior myocardial infarction patients (Cardiac Study).

AIMS: Bone marrow (BM) stem cells improve cardiac function and outcome after acute ST-segment elevation myocardial infarction (MI). In this randomized controlled trial, the effects of intracoronary transfer of autologous BM cells on left ventricular ejection fraction (LVEF) and volumes (2D-echo and resting SPECT), stroke volume [impedance cardiography (ICG)], autonomic control [heart rate variability (HRV)], baroreflex sensitivity (BRS), and exercise tolerance (cardiopulmonary exercise test) were assessed in post-MI patients. Exercise stress SPECT was also performed. METHODS AND RESULTS: After percutaneous coronary intervention (PCI), 38 patients with residual LV dysfunction were randomized to either the BM group (optimized treatment plus intracoronary transfer of autologous BM cells 4 + or - 1 days after PCI, n = 19) or control (C) group (optimized treatment only, n = 19). After 12 months, mean LVEF (%) increased 13.1 + or - 1.9 in the BM patients vs. 5.3 + or - 2.0 in C, with an increase in stroke volume (mL, 14.5 + or - 4.0 in BM vs. 1.8 + or - 3.7 in C) associated with improved HRV [SD (ms) 62.4 + or - 8.3 in BM vs. 19.0 + or - 7.5 in C), higher BRS (ms/mmHg, 8.0 + or - 1.8 in BM vs. -1.9 + or - 1.7 in C), and peak VO(2) (mL/kg min(-1), 3.5 + or - 1.0 in BM vs. -0.4 + or - 0.5 in C). Stress SPECT showed improvements in perfusion, regional and global LV function scores (P < 0.05 BM vs. C groups for all comparisons). Cell transfer did not increase the risk of adverse clinical, in-stent restenosis, or proarrhythmic events. CONCLUSION: The beneficial effect of autologous BM cells in post-MI patients with depressed LV function may be mediated by restoration of autonomic control, and improved exercise tolerance.