Skin-derived microorgan autotransplantation as a novel approach for therapeutic angiogenesis

Voisine, Pierre; Rosinberg, Audrey; Wykrzykowska, Joanna J.; Shamis, Yulia; Wu, Gui Fu; Appelbaum, Evan; Li, Jian; Sellke, Frank W.; Pinto, Duane S.; Gibson, C. Michael; Mitrani, Eduardo; Laham, Roger J.

doi:10.1152/ajpheart.00112.2007

Cited by 3 publications

(5 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Three weeks after treatment, morphometric analysis showed increased neovascularization with SMO treatment. Furthermore, SMO implantation resulted in significant improvement of lateral wall perfusion during pacing and significant increases in VEGF and CD31 expression in the ischemic area of treated animals (14).…”

Section: Resultsmentioning

confidence: 90%

“…The efficacy of skin‐derived MO (SMO) implantation in a porcine model of chronic myocardial ischemia was tested in 18 pigs that underwent placement of an ameroid constrictor on the proximal circumflex artery (14). Three weeks later, split‐thickness skin biopsies were harvested and pigs were randomized to lateral wall implantation of either 8 or 16 SMOs or blank injections.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Biopump: Autologous skin-derived micro-organ genetically engineered to provide sustained continuous secretion of therapeutic proteins

Mitrani

Pearlman²,

Stern³

et al. 2011

Dermatologic Therapy

Self Cite

View full text Add to dashboard Cite

A novel approach for sustained production of therapeutic proteins is described, using genetic modification of intact autologous micro-organ tissue explants from the subject's own skin. The skin-derived micro-organ can be maintained viable ex vivo for extended periods and is transduced with a transgene encoding a desired therapeutic protein, resulting in protein-secreting micro-organ (biopump (BP)). The daily protein production from each BP is quantified, enabling drug dosing by subcutaneous implantation of the requisite number of BPs into the patient to provide continuous production to the circulation of a known amount of the therapeutic protein. Each implanted BP remains localized and is accessible, to enable removal or ablation if needed. Examples from preclinical and clinical studies are presented, including use of associated virus vector 1 and helper-dependent adenoviral vectors producing BPs to provide long-term sustained secretion of recombinant interferon-α and erythropoietin.

show abstract

Section: Resultsmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Biopump: Autologous skin-derived micro-organ genetically engineered to provide sustained continuous secretion of therapeutic proteins

Mitrani

Pearlman²,

Stern³

et al. 2011

Dermatologic Therapy

Self Cite

View full text Add to dashboard Cite

show abstract

“…9,12 SMOs were found to retain those properties irrespective of whether they were derived from new born or adult skin even though they were cultured in serum-free medium. In the present work we show that in frog-derived SMOs, not only do epidermal cells continue to transcribe housekeeping and tissue-specific genes, but also that whole secretory glands remain functional for several days in culture.…”

Section: Discussionmentioning

confidence: 99%

“…9,10 Such fragments have been termed MOs to distinguish them from other tissue fragments that do not encompass the true organ structure. 9,11,12 In the present work we report the collection and initial characterization of activities of frogs collected from highly varied habitats of Colombia. In addition we have collected DNA and RNA samples from each species for our records and for further analysis.…”

Section: Introductionmentioning

confidence: 99%

Skin micro-organs from several frog species secrete a repertoire of powerful antimicrobials in culture

et al. 2012

Self Cite

View full text Add to dashboard Cite

This work is an attempt to take advantage of the rich biodiversity that exists in Colombia in order to start a systematic analysis of antimicrobial substances that have emerged through amphibian evolution. For this purpose we have developed a technique to grow intact frog skin derived micro-organs (SMOs) in vitro in the absence of serum. We show that in SMOs, the skin glands remain intact and continue to secrete into the medium substances with potent antibacterial activity, for several days in culture. Our strategy has been to create a bank of substances secreted by amphibian skin from different species. This bank contains at present around 50 species and is of particular importance as some of the species are in danger of disappearing. We show that some of the species tested displayed very strong antibacterial activity without being toxic to somatic cell lines, even at 10-fold higher concentration.

show abstract

“…Lastly, the effects of cardiomyotisue implantation can be contrasted with effect of skin microorgans transplantation 35. While skin microorgan implantation improved perfusion no effect on left ventricular function was observed.…”

Section: Discussionmentioning

confidence: 99%

Autologous Cardiomyotissue Implantation Promotes Myocardial Regeneration, Decreases Infarct Size, and Improves Left Ventricular Function

et al. 2011

Self Cite

View full text Add to dashboard Cite

Background-Cell therapy for myocardial infarction (MI) may be limited by poor cell survival and lack of transdifferentiation. We report a novel technique of implanting whole autologous myocardial tissue from preserved myocardial regions into infarcted regions. Methods and Results-Fourteen rats were used to optimize cardiomyotissue size with peritoneal wall implantation (300 m identified as optimal size). Thirty-nine pigs were used to investigate cardiomyotissue implantation in MI induced by left anterior descending balloon occlusion (10 animals died; male-to-female transplantation for tracking with in situ hybridization for Y chromosome, nϭ4 [2 donors and 2 MI animals]; acute MI implantation cohort at 1 hour, nϭ13; and healed MI implantation at 2 weeks, nϭ12 Key Words: myocardial infarction Ⅲ remodeling Ⅲ stem cells M yocardial infarction (MI) and its resultant left ventricular (LV) dysfunction remain a leading cause of mortality and morbidity. Different therapies for myocardial regeneration have been investigated with varying results and no definitive beneficial effects. [1][2][3][4][5][6][7][8][9][10][11] Concomitantly, the intrinsic regenerative potential of the myocardium has been increasingly recognized. [12][13][14] Adult cardiac stem cells injected into vasculature of rats after MI are able to differentiate into cardiomyocytes and arterioles. 15,16 In addition, it has been increasingly recognized that the delivery modality is a key limiting step in attempts at myocardial regeneration and angiogenesis with poor survival of transplanted cells (possible related to "milieu") and limited deposition and retention of injected cytokines. [17][18][19][20] This, coupled with mounting evidence relative to the lack of transdifferentiation potential of adult non-cardiac-derived stem cells, warrants a novel approach to myocardial regeneration. 21,22 Clinical Perspective on p 69We have developed a novel approach to adult cardiomyocyte transplantation. In a porcine model of MI, core biopsies of myocardial tissue are obtained from the preserved basal ventricular septum and used for implantation into the myocardial scar Received January 28, 2006; accepted October 8, 2010 MethodsAll experiments were performed in accordance with National Institutes of Health guidelines and were approved by the Institutional Animal Care and Use Committee at Beth Israel Deaconess Medical Center. Myotissue Sizing ExperimentsFourteen inbred rats (50 to 60 g) were used. Donor rats (nϭ3) were euthanized with CO 2 inhalation, and the heart was excised and placed in normal saline. Strips of varying diameters (100 to 500 mol/L) were obtained under a dissecting microscope. Eleven rats were then anesthetized with intraperitoneal ketamine/xylaxine (0.1 mL /100 g). The abdominal skin was incised and rectus muscle was exposed. Strips were implanted, and rectus fascia was closed with 10 -0 Prolene suture. Animals were divided into 5 groups (nϭ2 per group) with implantation of 100-, 200-, 300-, 400-, and 500-m strips (1 strip per animal). The animals were ...

show abstract

Skin-derived microorgan autotransplantation as a novel approach for therapeutic angiogenesis

Cited by 3 publications

References 28 publications

Biopump: Autologous skin-derived micro-organ genetically engineered to provide sustained continuous secretion of therapeutic proteins

Biopump: Autologous skin-derived micro-organ genetically engineered to provide sustained continuous secretion of therapeutic proteins

Skin micro-organs from several frog species secrete a repertoire of powerful antimicrobials in culture

Autologous Cardiomyotissue Implantation Promotes Myocardial Regeneration, Decreases Infarct Size, and Improves Left Ventricular Function

Contact Info

Product

Resources

About