Abdominal Pocket Method as a Salvage Procedure for Vascular Insufficiency After Distal Digital Replantation.

PURPOSE: To assess the utility of abdominal pocketing of a deepithelialized reattached digit to allow for neovascularization as a salvage procedure for circulatory insufficiency after digital replantation. We performed this method in Tamai zone II cases in which microsurgical vascular anastomosis was expected to be difficult based on the findings at the initial operation. MATERIALS AND METHODS: From 2008 to 2014, 5 injured digits from 5 patients (mean age, 34 years; range: 25-54 years) underwent the abdominal pocket method as a salvage procedure for postoperative circulatory insufficiency. We evaluated the survival incidence, the timing between operations, and the duration of the second operation. During this study period, 7 amputated digits from 7 patients underwent vascular reanastomosis. We also evaluated the survival incidence for these cases. RESULTS: Four out of 5 replanted digital tips survived. The mean time between the initial operation and the onset of vascular problems was 82 hours, and the mean duration of the second operation was 48 minutes. The survival incidence for reanastomosed cases was 6 out of 7. CONCLUSIONS: The abdominal pocket method is useful for treating circulatory insufficiency after digital replantation in Tamai zone II cases in which microsurgical vascular reanastomosis was expected to be difficult based on the findings at the initial operation. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Micronized cellular adipose matrix purified with a bladed connector contains abundant functional adipose stem cells.

INTRODUCTION: A specialized device equipped with a sharp blade filter has been developed to enable more efficient purification of a micronized cellular adipose matrix (MCAM) containing stem cells. The aim of this study is to compare the characteristics and functions of the population of stromal cells (mSVF) and cultured cells (mASCs) purified using this device with those of cSVF and cASCs obtained through conventional enzymatic purification. METHODS: Cell viability, proliferation capacity and yield were assessed. Characterization of stem cell potency was performed by analyzing cell surface markers including CD34, a marker of activated adipose-derived stem cells. The trilineage differentiation potential was evaluated using RT-PCR and histology. RESULTS: The yield rate of mSVF obtained from MCAM was significantly higher than that with the conventional method, although use of the device resulted in a slight decrease in cell viability. After culture, mASCs exhibited a remarkable clonogenic potential and significantly higher cell proliferation potential than cASCs. The mASCs also displayed a distinct pattern of ASC cell surface markers, increased expression of genes related to CD34, high pluripotency, and a high trilineage differentiation ability. CONCLUSION: The specialized device enhanced the yield of SVF and produced cells with high proliferation rates and characteristics that include expression of stem cell markers.

Micronized Cellular Adipose Matrix Promotes the Therapeutic Effect of an Artificial Nerve Conduit in Peripheral Nerve Gap Injury.

BACKGROUND: Stromal vascular fraction (SVF) isolated from adipose tissue has been shown to be beneficial for treating peripheral nerve injuries. Micronized cellular adipose matrix (MCAM) is an SVF-rich micronized fat tissue obtained by a series of simple mechanical processes. This study assessed the therapeutic effect of MCAM for peripheral nerve injury. METHODS: Microscopic evaluation of the cell phenotype and functions was performed to determine the adipose-derived stem cell content of the MCAM. An artificial nerve conduit (ANC) filled with MCAM was implanted into a sciatic nerve defect in immunodeficient mice. Comparisons of this treatment with an autograft, an ANC filled with SVF cells, and an ANC alone were made based on electrophysiologic characteristics, Sciatic Functional Index, and histologic analyses of regenerated nerve fiber and myelination using electron microscopy, and the preventive effect on innervated muscle atrophy. RESULTS: MCAM contained many cells with a phenotype and differentiation potency similar to those of ADSCs. The implantation experiment indicated that MCAM enhanced the efficiency of functional and structural recovery and prevented atrophy of the innervated muscle. These effects were significantly improved compared with the control group (ANC only) and comparable to those in the SVF group, whereas the improvement did not reach the same level of the autograft group. CONCLUSION: Injection of MCAM into an ANC accelerated nerve regeneration compared with use of an ANC alone, which indicates that MCAM is a promising transplant material for treatment of peripheral nerve injury and an alternative to use of SVF cells. CLINICAL RELEVANCE STATEMENT: Micronized cellular adipose matrix, which can be harvested and isolated from adipose tissue with a simple device, has been shown for the first time to be highly useful as an implantable material for new peripheral nerve regeneration.

Direct Conversion of Human Fibroblasts into Adipocytes Using a Novel Small Molecular Compound: Implications for Regenerative Therapy for Adipose Tissue Defects.

There is a need in plastic surgery to prepare autologous adipocytes that can be transplanted in patients to reconstruct soft tissue defects caused by tumor resection, including breast cancer, and by trauma and other diseases. Direct conversion of somatic cells into adipocytes may allow sufficient functional adipocytes to be obtained for use in regeneration therapy. Chemical libraries of 10,800 molecules were screened for the ability to induce lipid accumulation in human dermal fibroblasts (HDFs) in culture. Chemical compound-mediated directly converted adipocytes (CCCAs) were characterized by lipid staining, immunostaining, and qRT-PCR, and were also tested for adipokine secretion and glucose uptake. CCCAs were also implanted into mice to examine their distribution in vivo. STK287794 was identified as a small molecule that induced the accumulation of lipid droplets in HDFs. CCCAs expressed adipocyte-related genes, secreted adiponectin and leptin, and abundantly incorporated glucose. After implantation in mice, CCCAs resided in granulation tissue and remained adipose-like. HDFs were successfully converted into adipocytes by adding a single chemical compound, STK287794. C/EBPα and PPARγ were upregulated in STK287794-treated cells, which strongly suggests involvement of these adipocyte-related transcription factors in the chemical direct conversion. Our method may be useful for the preparation of autogenous adipocytes for transplantation therapy for soft tissue defects and fat tissue atrophy.

ALK5 i II Accelerates Induction of Adipose-Derived Stem Cells toward Schwann Cells through a Non-Smad Signaling Pathway.

Schwann cells (SCs) are likely to be a vital component of cell-based therapies for nerve regeneration. There are various methods for inducing SC-like cells (SCLCs) from adipose-derived stem cells (ADSCs), but their phenotypic and functional characteristics remain unsatisfactory. Here, we report a novel efficient procedure to induce SCLCs by culturing ADSCs with ALK5 inhibitor (ALK5 i) II, a specific inhibitor of activin-like kinase 5 (ALK5) (transforming growth factor-ß receptor 1 (TGFßR1)) that is also known as Repsox. The resultant cells that we named "modified SCLCs (mSCLCs)" expressed SC-specific genes more strongly than conventional SCLCs (cSCLCs) and displayed a neurosupportive capacity in vitro, similarly to genuine SCs. Regarding the mechanism of the mSCLC induction by ALK5 i II, knockdown of Smad2 and Smad3, key proteins in the TGFß/Smad signaling pathway, did not induce SC markers. Meanwhile, expression of multipotent stem cell markers such as Sex-determining region Y- (SRY-) box 2 (Sox2) was upregulated during induction. These findings imply that ALK5 i II exerts its effect via the non-Smad pathway and following upregulation of undifferentiated cell-related genes such as Sox2. The procedure described here results in highly efficient induction of ADSCs into transgene-free and highly functional SCLCs. This approach might be applicable to regeneration therapy for peripheral nerve injury.

[Bi-weekly chemotherapy with medium-dose docetaxel for advanced and recurrent breast cancers (The 15th study of Keiji Breast Cancer Study Group)].

The efficacy and safety of bi-weekly administration of medium-dose docetaxel (TXT) were evaluated in patients with advanced and recurrent breast cancers. The additional effect of 5'-DFUR for non-responders was also evaluated. Forty patients with advanced and recurrent breast cancers were treated and 38 cases of 40 were evaluated (34 with recurrent cases and 4 with advanced cases). All cases were female, and their mean age was 56.0 (38-74). TXT of 60 mg/body, which was equivalent to 30-50 mg/m2 for standard-sized Japanese women, was administered every two weeks. 5'-DFUR of 800 mg/body was added for non-responders after 5 weeks. The response rate was calculated from the data of 32 cases with measurable lesions, and side effects were evaluated in about 34 cases with exact records. Two hundred seventy-one courses were performed for 38 patients (4-24 courses per person, average 7.13 courses). The mean dosage per course of TXT was 58.4 mg/body (38.3 mg/ m2). Three complete and 7 partial responses were observed (overall response rate: 31.3%). Ten non-responders were evaluated for the additional effect of 5' DFUR, and one case reached PR. Grade 3/4 bone marrow suppression occurred in 9 patients, and Grade 3/4 general malaise was observed in two patient. According to the results, bi-weekly administration of medium dose TXT is an active and safe regimen in patients with advanced and recurrent breast cancers. The additional effect of 5'-DFUR was observed in one of 10 non-responders of bi-weekly chemotherapy with medium-dose TXT.

No increase of breast cancer incidence in Japanese women who received hormone replacement therapy: overview of a case-control study of breast cancer risk in Japan.

Hormone replacement therapy (HRT) has been considered one of the main risk factors for breast cancer. Studies demonstrating the relationship between HRT and breast cancer incidence were conducted in Western countries and the target populations were mainly Caucasians. Since the Women's Health Initiatives demonstrated that HRT increased the risk of breast cancer with statistical significance, the number of HRT users in the United States has dramatically decreased. A recent case-control study has investigated the relationship between HRT and breast cancer in Japan, and here we review the results of this study to compare any discrepancy in breast cancer risk between Japanese and Western populations. For this case-control study, at seven institutions, women between the ages of 45 through 69 years, with histologically confirmed breast cancer, were selected as the case group. An age-adjusted control group was selected, using hospital-based data, including records of those screened for lung, gastrointestinal, and gynecological cancer. Questionnaires were administered, and items questioned included various factors related to the incidence of breast cancer: age at diagnosis, body mass index (BMI), smoking habit, age at menopause, birth history, number of births, number of children, history of breast feeding, familial background, and menopausal status. In total, 6183 samples (98.4% of the estimated samples) were put into the database. Data from 276 samples were excluded due to ineligibility. Finally, 5861 samples (3434 cases and 2427 controls) were analyzed. In 3316 cases, 164 (5.0%) patients received hormone-replacement therapy (HRT); on the other hand, 253 (10.7%) of 2355 controls received HRT. The odds ratio was 0.432 (95% confidence intervals [CI], 0.352-0.53), and there was a significantly negative correlation between HRT use and breast cancer. The risk factors in Japanese women showed similar profiles to those in women in Western countries. However, we did find some different profiles of breast cancer risk in the Japanese women. Changing of lifestyle may increase breast cancer risk in Japan.