Low-molecular weight heparin protamine complex augmented the potential of adipose-derived stromal cells to ameliorate limb ischemia

Kishimoto, Satoko; Inoue, Kazuhiro; Nakamura, Shingo; Hattori, Hidemi; Sakuma, Masashi; Toyoda, Shigeru; Iwaguro, Hideki; Tanaka, Isao; Inoue, Teruo; Yoshida, Keisuke

doi:10.1016/j.atherosclerosis.2016.04.003

Cited by 16 publications

(19 citation statements)

References 38 publications

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“…For qualitative histological analysis, we used BZ-X700 microscope (Keyence, Osaka, Japan) to capture images. α-SMA-positive area and M-T-positive area were quantified as the percentage of the total tissue area in a high power field (400×) using Adobe Photoshop CS6 (Adobe Systems, San Jose, CA, USA) [19] . A threshold was selected and used to identify positive pixels on each slide.…”

Section: Methodsmentioning

confidence: 99%

Autologous and heterotopic transplantation of adipose stromal vascular fraction ameliorates stress urinary incontinence in rats with simulated childbirth trauma

Inoue

Kishimoto

Kaga

et al. 2018

Regenerative Therapy

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IntroductionAutologous transplantation of adipose stromal vascular fraction (SVF) is a cost-effective and technically accessible option for cell therapy. Clinical study of SVF transplantation for male stress urinary incontinence (SUI) is underway, but the effectiveness remains unknown for female SUI, majority of which is caused by childbirth trauma.MethodsVaginal Distension (VD) rats were generated as in vivo model for female SUI. To quantitate the severity of SUI, leak point pressure (LPP) was measured by placing a bladder catheter. There was a characteristic waveform of LPP with two-peaks, and we counted the second peak as an LPP value. Adipose SVF was separated from inguinal fat and delivered into external urethral sphincter (EUS) through transperineal injection. LPP was measured 7 or 14 days after SVF transplantation. Tissue damage and collagen synthesis around the EUS were visualized by Masson's trichrome and eosin staining. Antibody against α-smooth muscle actin (α-SMA) was used to stain smooth muscle or activated stromal cells. Donor SVF cells were distinguished from recipient EUS tissue by tracking with GFP transgene.ResultsVD procedure decreased the frequency at which the normal LPP waveform appeared and lowered the LPP value. SVF injection normalized the waveform as well as the level of LPP. VD disrupted histological structure of EUS and SVF failed to differentiate into striatal muscles. Instead, SVF increased α-SMA positive cells and collagen synthesis but the phenomena depended on VD stimulus. GFP tracking indicated that the transplanted SVF cells persisted for four weeks and synthesized α-SMA protein simultaneously.ConclusionsAutologous transplantation of adipose SVF displayed bulking effects through collagen synthesis. However, such heterotopic activation was dependent on tissue damage.

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Section: Methodsmentioning

confidence: 99%

Autologous and heterotopic transplantation of adipose stromal vascular fraction ameliorates stress urinary incontinence in rats with simulated childbirth trauma

Inoue

Kishimoto

Kaga

et al. 2018

Regenerative Therapy

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“…An improvement in cell survival, cell retention and upregulation of proangiogenic factors was observed compared to that of transplants of a monolayer ADSC (control). Recently, aggregates of ADSCs (4 × 10 6 cells) and heparin/protamine nanoparticles (ADSC/LH/P‐NP) were transplanted into mice ischemic hindlimbs for therapeutic angiogenesis . At 14 d post transplantation, there was no evidence of tissue necrosis, and blood perfusion was recovered in ADSC/LH/P‐NP groups when compared to that of control groups (contralateral nonischemic limb).…”

Section: Application Of Nanoparticles For the Treatment Of Padmentioning

confidence: 99%

Nanoparticles for Detection and Treatment of Peripheral Arterial Disease

Noukeu

Wolf

Yuan

et al. 2018

Small

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Peripheral arterial disease (PAD) is defined as a slow, progressive disorder of the lower extremity arterial vessels characterized by chronic narrowing that often results in occlusion and is associated with loss of functional capacity. Although the PAD occurrence rate is increasing in the elderly population, outcomes with current treatment strategies are suboptimal. Hence, there is an urgent need to develop new technologies that overcome limitations of traditional modalities for PAD detection and therapy. In this Review, the application of nanotechnology as a tool that bridges the gap in PAD diagnosis and therapy is in focus. Several materials including synthetic, natural, biodegradable, and biocompatible materials are used to develop nanoparticles for PAD diagnostic and/or therapeutic applications. Moreover, various recent research approaches are being explored to diagnose PAD through multimodality imaging with different nanoplatforms. Further efforts include targeted delivery of various therapeutic agents using nanostructures as carriers to treat PAD. Last, but not least, despite being a fairly new field, researchers are exploring the use of nanotheranostics for PAD detection and therapy.

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“…The self-assembling peptide RADA 16, modified by covalent immobilization of P substance, resulted in the recruitment of MSCs in the HLI region, followed by neovascularization . When loaded into a low-molecular-weight heparinprotamine complex, adipose-derived stem cells exhibited significant cell-cell interaction and improved cell viability, which may help to effectively rescue the limb from ischemia (Kishimoto et al 2016).…”

Section: Nanocarriers In Hlimentioning

confidence: 99%

Trimodal rescue of hind limb ischemia with growth factors, cells, and nanocarriers: fundamentals to clinical trials

Lakshmanan

Ukani

Rishi

et al. 2017

Can. J. Physiol. Pharmacol.

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Peripheral artery disease is a severe medical condition commonly characterized by critical or acute limb ischemia. Gradual accumulation of thrombotic plaques in peripheral arteries of the lower limb may lead to intermittent claudication or ischemia in muscle tissue. Ischemic muscle tissue with lesions may become infected, resulting in a non-healing wound. Stable progression of the non-healing wound associated with severe ischemia might lead to functional deterioration of the limb, which, depending on the severity, can result in amputation. Immediate rescue of ischemic muscles through revascularization strategies is considered the gold standard to treat critical limb ischemia. Growth factors offer multiple levels of protection in revascularization of ischemic tissue. In this review, the basic mechanism through which growth factors exert their beneficial properties to rescue the ischemic limb is extensively discussed. Moreover, clinical trials based on growth factor and stem cell therapy to treat critical limb ischemia are considered. The clinical utility of stem cell therapy for the treatment of limb ischemia is explained and recent advances in nanocarrier technology for selective growth factor and stem cell supplementation are summarized.

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Low-molecular weight heparin protamine complex augmented the potential of adipose-derived stromal cells to ameliorate limb ischemia

Abstract: The LH/P-MPs augmented the effects of ADSCs on angiogenesis and reversal of limb ischemia. Use of ADSC/LH/P-MP aggregates offers a novel and convenient treatment method and potentially represents a promising new therapeutic approach to inducing angiogenesis in ischemic diseases.

Cited by 16 publications

References 38 publications

Autologous and heterotopic transplantation of adipose stromal vascular fraction ameliorates stress urinary incontinence in rats with simulated childbirth trauma

Autologous and heterotopic transplantation of adipose stromal vascular fraction ameliorates stress urinary incontinence in rats with simulated childbirth trauma

Nanoparticles for Detection and Treatment of Peripheral Arterial Disease

Trimodal rescue of hind limb ischemia with growth factors, cells, and nanocarriers: fundamentals to clinical trials

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