Unblinded Pilot Study of Autologous Transplantation of Bone Marrow Mononuclear Cells in Patients With Thromboangiitis Obliterans

Abstract

Background-The short-term clinical benefits of bone marrow mononuclear cell transplantation have been shown in patients with critical limb ischemia. The purpose of this study was to assess the long-term safety and efficacy of bone marrow mononuclear cell transplantation in patients with thromboangiitis obliterans. Methods and Results-Eleven limbs (3 with rest pain and 8 with an ischemic ulcer) of 8 patients were treated by bone marrow mononuclear cell transplantation. The patients were followed up for clinical events for a mean of 684Ϯ549 days (range 103 to 1466 days). At 4 weeks, improvement in pain was observed in all 11 limbs, with complete relief in 4 (36%). Pain scale (visual analog scale) score decreased from 5.1Ϯ0.7 to 1.5Ϯ1.3. An improvement in skin ulcers was observed in all 8 limbs with an ischemic ulcer, with complete healing in 7 (88%). During the follow-up, however, clinical events occurred in 4 of the 8 patients. The first patient suffered sudden death at 20 months after transplantation at 30 years of age. The second patient with an incomplete healing of a skin ulcer showed worsening of the lesion at 4 months. The third patient showed worsening of rest pain at 8 months. The last patient developed an arteriovenous shunt in the foot at 7 months, which spontaneously regressed by 1 year. Conclusions-In the present unblinded and uncontrolled pilot study, long-term adverse events, including death and unfavorable angiogenesis, were observed in half of the patients receiving bone marrow mononuclear cell transplantation. Given the current incomplete knowledge of the safety and efficacy of this strategy, careful long-term monitoring is required for future patients receiving this treatment.

A Five-Year Study of the Efficacy of Purified CD34+ Cell Therapy for Angiitis-Induced No-Option Critical Limb Ischemia

“…Many studies using different methods, such as vascular endothelial growth factor (VEGF)‐related gene transfer 6, 7, bone‐marrow mononuclear cell (BMMNC) 8, 9, 10, 11, 12, PBMNC 13, 14, 15, 16, 17, 18, or CD34+ cell 2, 3, 4 transplantation, have been completed and have proven their safety and efficacy. The long‐term outcome after CD34+ cell therapy in CLI patients was already reported by Kinoshita et al in 2012 19.…”

Emerging hurdles in stem cell therapy for peripheral vascular disease

“…Overall, clinical results show feasibility and safety (at least in the short term) and indicate an encouraging effect when comparing the patient's status before and after transplantation (Table 1a-c). Noteworthy, however, one study with TAO patients reported a high incidence of adverse effects in the long term (sudden death, worsening of ischemic ulcers or rest pain, development of an arteriovenous shunt) [12], and two other studies (one in patients with a high number of risk factors and one in CTD patients) reported that positive effects may not apply to all patient categories [11,13] (Table 1a-b).…”

Thérapies cellulaires pro-angiogéniques dans le traitement des pathologies ischémiques

“…Les autres types de cellules souches adultes requièrent une étape d'amplification ex vivo, ce qui impose un délai entre le moment du prélèvement et l'administration des cellules. Une alternative serait de [26,27]. Cependant, un certain nombre de ces patients présentent des effets secondaires, et l'amélio-ration n'est souvent que transitoire [27].…”

“…Une alternative serait de [26,27]. Cependant, un certain nombre de ces patients présentent des effets secondaires, et l'amélio-ration n'est souvent que transitoire [27]. De même, la transplantation par voie intracoronaire de cellules mononucléées médullaires dans le myocarde de patients ayant une ischémie aiguë augmente la perfusion et la fonction du tissu ischémié [28][29][30].…”