The stromal vascular fraction (SVF) of adipose tissue is known to contain mesenchymal stem cells (MSC), T regulatory cells, endothelial precursor cells, preadipocytes, as well as anti-inflammatory M2 macrophages. Safety of autologous adipose tissue implantation is supported by extensive use of this procedure in cosmetic surgery, as well as by ongoing studies using in vitro expanded adipose derived MSC. Equine and canine studies demonstrating anti-inflammatory and regenerative effects of non-expanded SVF cells have yielded promising results. Although non-expanded SVF cells have been used successfully in accelerating healing of Crohn's fistulas, to our knowledge clinical use of these cells for systemic immune modulation has not been reported. In this communication we discuss the rationale for use of autologous SVF in treatment of multiple sclerosis and describe our experiences with three patients. Based on this rationale and initial experiences, we propose controlled trials of autologous SVF in various inflammatory conditions.

No abstract

Cellular therapy for spinal cord injury (SCI) is overviewed focusing on bone marrow mononuclear cells, olfactory ensheathing cells, and mesenchymal stem cells. A case is made for the possibility of combining cell types, as well as for allogeneic use. We report the case of 29 year old male who suffered a crush fracture of the L1 vertebral body, lacking lower sensorimotor function, being a score A on the ASIA scale. Stem cell therapy comprised of intrathecal administration of allogeneic umbilical cord blood ex-vivo expanded CD34 and umbilical cord matrix MSC was performed 5 months, 8 months, and 14 months after injury. Cell administration was well tolerated with no adverse effects observed. Neuropathic pain subsided from intermittent 10/10 to once a week 3/10 VAS. Recovery of muscle, bowel and sexual function was noted, along with a decrease in ASIA score to "D". This case supports further investigation into allogeneic-based stem cell therapies for SCI.

Patients with congestive heart failure (CHF) that are not eligible for transplantation have limited therapeutic options. Stem cell therapy such as autologous bone marrow, mobilized peripheral blood, or purified cells thereof has been used clinically since 2001. To date over 1000 patients have received cellular therapy as part of randomized trials, with the general consensus being that a moderate but statistically significant benefit occurs. Therefore, one of the important next steps in the field is optimization. In this paper we discuss three ways to approach this issue: a) increasing stem cell migration to the heart; b) augmenting stem cell activity; and c) combining existing stem cell therapies to recapitulate a "therapeutic niche". We conclude by describing a case report of a heart failure patient treated with a combination stem cell protocol in an attempt to augment beneficial aspects of cord blood CD34 cells and mesenchymal-like stem cells.

No abstract

No abstract

No abstract

Aim: To evaluate the efficacy of Lenalidomide (Len) as compassionate use in relapsed or progressive Multiple Myeloma (MM) up to its approval in Spain. Patients and Methods: GEM-PETHEMA designed a transverse and retrospective, multicenter analysis of MM cases which Len compassionate use was requested until December, 2007. The decision to treat these patients was previous and independent from the decision to conduct the present analysis and depended only on the clinical criteria of the responsible doctors. At least, one response assessment was a must for efficacy analysis. Results: 111 MM patients have been included. Eligible patients for efficacy were 103. Mean age was 65.7 (38–85); 53 m, 50 f. Previous median lines of therapy were 3 (1–8): 92 (89.3%) have received bortezomib; 37 (35.9%) autologous PBSCT and 26 (25.2%) thalidomide. Extramedullary plasmocitomas were present in 25 (24.3%). Mean Len dose was 22.8 mg (± 4.9): 82 (79.6%) received the standard dose and schedule (25 mg d for 3 w every 4 w) and 21 (20.4%) received less dose and/or different schedule. 92 (89.3%) received Dexametasone (mean dose 58.33 mg/w) [± 35.8]). Response: 4 (3.9%) sCR, 11 CR (10.7%), 12 VGPR (11.7%), 41 PR (39.8%), 20 SD (19.4%), 13 PD (12.6%), 2 NE (1.9). Among groups, response equal or superior to PR was observed in all settings: 64.1% in prior exposed to bortezomib, 46.1% in prior exposed to thalidomide and 40.0% in patients with extramedullary plasmocitomas. Previous transplant, the number of previous lines received, renal failure, age, or cytogenetic did not affect significantly the overall response rate. Median duration of treatment was 7.7 m (1–21); median TTP was 8.3 m and median global survival since starting Len therapy was 11 m (6–22). Median survival since diagnostic was 49 m (40–60). At the time of analysis, 46 (45.5%) patients were still on Len therapy, and 72 (79.6%) were alive. Toxicity: ≥ grade II: neutropenia, 51 (46.4%); thrombocytopenia, 39 (35.5%); DVT, 5 (4.5%); rash, 3 (2.7%); neutropenic fever, 8 (7.3%); others, 13 (11.8%). DVT/PE prophylaxis was used in 89 (86.4%) patients: LWMH in 43.8 % and low dose aspirin in 48.3 %. No PE was reported. Conclusions: Lenalidomide is effective in this heavily pre-treated MM population-progressive or refractory to standard therapy-even in different clinical settings. The most frequent association to Len was intermediate dose of Dex. Although response rate was superior in patients exposed previously to bortezomib, no differences on duration and survival were observed. Patients with extramedullary plasmocitomas showed also response. Toxicity, mainly myelosupression was predictable and manageable with dose adjustments and cytokine support.