Bio

Bio


I am an Instructor in the Department of Cardiothoracic Surgery and the Cardiovascular Institute at Stanford University working with Dr. Ngan Huang using spatially patterned biomimetic niches to direct cell fate, angiogenesis, and tissue regeneration. Prior to Stanford, I attained a PhD from the University of California, Davis in Biomedical Engineering in the translational laboratory of Dr. Alice Tarantal working towards regenerative therapies for congenital kidney diseases using decellularized kidney matrices and directed differentiation of stem and progenitor cells towards renal lineages.

I am dedicated to understanding the biomechanical cell-substrate interactions that modulate cell phenotype and behavior towards enhancing tissue neurovascularization, regeneration, and function. The overarching goal of my research is the development of bioengineered therapeutics that can lead to future regenerative therapies, with relevance to cardiovascular and musculoskeletal injuries and diseases. My work to date, suggests that the composition, spatial organization, and mechanical properties of extracellular matrix microenvironments play a directive role in modulating cell phenotype and function. The scientific themes that frame my research program are the elucidation of novel biomechanical pathways that can be harnessed to enhance engineered vasculature, innervation, and function of cardiac and skeletal muscle, and complex multi-tissue composites using methods that range from nanopatterning of biomaterials and RNASeq, to modular immuno-physiologic culture systems and regenerative rehabilitation.

My research background spans the fields of biomedical engineering, developmental and stem cell biology, and cardiovascular medicine, making multi-disciplinary research at the interface of these disciplines natural and primed for innovation. I have enjoyed research funding through the California Institute of Regenerative Medicine (CIRM), the NIH/NHLBI (T32 and F32 fellowships), and the American Heart Association. I recently received K99/R00 funding through the NIH/NHLBI and look forward to using this award to jumpstart my independent research career.

I am eager to mentor undergraduates, graduate students, and postdocs from diverse backgrounds into critically thinking ambassadors of science, engineering, and medicine. I am excited to share my knowledge and passion for science and engineering with this next generation of talented young innovators and to be a positive force in promoting equity in education and diversity in STEM fields.

Academic Appointments


Honors & Awards


  • Career Development Award: K99/R00 NIH Pathway to Independence Award, NIH/NHLBI (1/15/18-12/31/22)
  • Pilot Training Grant: Alliance for Regenerative Rehabilitation Research, AR3T (7/1/17-6/30/19)
  • Postdoctoral Fellowship: F32 Ruth L. Kirschstein National Research Service Award (NRSA), NIH/NHLBI (9/1/16-1/14/18)
  • Postdoctoral Fellowship: AHA Western States Affiliates Postdoctoral Fellowship, AHA (7/1/15 – 8/31/16)
  • Postdoctoral Fellowship: T32 Stanford Cardiovascular Institute Training Grant, NIH/NHLBI (7/1/14 – 6/30/15)
  • Pre-doctoral Fellowship: California Institute of Regenerative Medicine Stem Cell Training Program, CIRM (9/1/08-8/31/11)
  • Pre-doctoral Fellowship: T32 Pre-Doctoral Clinical Research Training Program, UC Davis, Clinical and Translational Science Center (4/1/08-8/31/08)

Professional Education


  • Ph.D., University of California, Davis, Biomedical Engineering (2012)
  • B.S., University of California, San Diego, Bioengineering (2007)

Publications

All Publications


  • Engineering Biomimetic Materials for Skeletal Muscle Repair and Regeneration. Advanced healthcare materials Nakayama, K. H., Shayan, M., Huang, N. F. 2019: e1801168

    Abstract

    Although skeletal muscle is highly regenerative following injury or disease, endogenous self-regeneration is severely impaired in conditions of volume traumatic muscle loss. Consequently, tissue engineering approaches are a promising means to regenerate skeletal muscle. Biological scaffolds serve as not only structural support for the promotion of cellular ingrowth but also impart potent modulatory signaling cues that may be beneficial for tissue regeneration. In this work, the progress of tissue engineering approaches for skeletal muscle engineering and regeneration is overviewed, with a focus on the techniques to create biomimetic engineered tissue using extracellular cues. These factors include mechanical and electrical stimulation, geometric patterning, and delivery of growth factors or other bioactive molecules. The progress of evaluating the therapeutic efficacy of these approaches in preclinical models of muscle injury is further discussed.

    View details for PubMedID 30725530

  • Rehabilitative exercise and spatially patterned nanofibrillar scaffolds enhance vascularization and innervation following volumetric muscle loss NPJ REGENERATIVE MEDICINE Nakayama, K. H., Alcazar, C., Yang, G., Quarta, M., Paine, P., Doan, L., Davies, A., Rando, T. A., Huang, N. F. 2018; 3: 16

    Abstract

    Muscle regeneration can be permanently impaired by traumatic injuries, despite the high regenerative capacity of skeletal muscle. Implantation of engineered biomimetic scaffolds to the site of muscle ablation may serve as an attractive off-the-shelf therapeutic approach. The objective of the study was to histologically assess the therapeutic benefit of a three-dimensional spatially patterned collagen scaffold, in conjunction with rehabilitative exercise, for treatment of volumetric muscle loss. To mimic the physiologic organization of skeletal muscle, which is generally composed of myofibers aligned in parallel, three-dimensional parallel-aligned nanofibrillar collagen scaffolds were fabricated. When implanted into the ablated murine tibialis anterior muscle, the aligned nanofibrillar scaffolds, in conjunction with voluntary caged wheel exercise, significantly improved the density of perfused microvessels, in comparison to treatments of the randomly oriented nanofibrillar scaffold, decellularized scaffold, or in the untreated control group. The abundance of neuromuscular junctions was 19-fold higher when treated with aligned nanofibrillar scaffolds in conjunction with exercise, in comparison to treatment of aligned scaffold without exercise. Although, the density of de novo myofibers was not significantly improved by aligned scaffolds, regardless of exercise activity, the cross-sectional area of regenerating myofibers was increased by > 60% when treated with either aligned and randomly oriented scaffolds, in comparison to treatment of decellularized scaffold or untreated controls. These findings demonstrate that voluntary exercise improved the regenerative effect of aligned scaffolds by augmenting neurovascularization, and have important implications in the design of engineered biomimetic scaffolds for treatment of traumatic muscle injury.

    View details for PubMedID 30245849

  • Big bottlenecks in cardiovascular tissue engineering. Communications biology Huang, N. F., Serpooshan, V., Morris, V. B., Sayed, N., Pardon, G., Abilez, O. J., Nakayama, K. H., Pruitt, B. L., Wu, S. M., Yoon, Y., Zhang, J., Wu, J. C. 2018; 1: 199

    Abstract

    Although tissue engineering using human-induced pluripotent stem cells is a promising approach for treatment of cardiovascular diseases, some limiting factors include the survival, electrical integration, maturity, scalability, and immune response of three-dimensional (3D) engineered tissues. Here we discuss these important roadblocks facing the tissue engineering field and suggest potential approaches to overcome these challenges.

    View details for PubMedID 30480100

  • Anisotropic microfibrous scaffolds enhance the organization and function of cardiomyocytes derived from induced pluripotent stem cells. Biomaterials science Wanjare, M., Hou, L., Nakayama, K. H., Kim, J. J., Mezak, N. P., Abilez, O. J., Tzatzalos, E., Wu, J. C., Huang, N. F. 2017; 5 (8): 1567–78

    Abstract

    Engineering of myocardial tissue constructs is a promising approach for treatment of coronary heart disease. To engineer myocardial tissues that better mimic the highly ordered physiological arrangement and function of native cardiomyocytes, we generated electrospun microfibrous polycaprolactone scaffolds with either randomly oriented (14 μm fiber diameter) or parallel-aligned (7 μm fiber diameter) microfiber arrangement and co-seeded the scaffolds with human induced pluripotent stem cell-derived cardiomyocytes (iCMs) and endothelial cells (iECs) for up to 12 days after iCM seeding. Here we demonstrated that aligned microfibrous scaffolds induced iCM alignment along the direction of the aligned microfibers after 2 days of iCM seeding, as well as promoted greater iCM maturation by increasing the sarcomeric length and gene expression of myosin heavy chain adult isoform (MYH7), in comparison to randomly oriented scaffolds. Furthermore, the benefit of scaffold anisotropy was evident in the significantly higher maximum contraction velocity of iCMs on the aligned scaffolds, compared to randomly oriented scaffolds, at 12 days of culture. Co-seeding of iCMs with iECs led to reduced contractility, compared to when iCMs were seeded alone. These findings demonstrate a dominant role of scaffold anisotropy in engineering cardiovascular tissues that maintain iCM organization and contractile function.

    View details for PubMedID 28715029

    View details for PubMedCentralID PMC5567776

  • Targeted delivery of human iPS-ECs overexpressing IL-8 receptors inhibits neointimal and inflammatory responses to vascular injury in the rat. American journal of physiology. Heart and circulatory physiology Giordano, S., Zhao, X., Xing, D., Hage, F., Oparil, S., Cooke, J. P., Lee, J., Nakayama, K. H., Huang, N. F., Chen, Y. 2016; 310 (6): H705-15

    Abstract

    Interleukin-8 (IL8) is highly expressed by injured arteries in a variety of diseases and is a chemoattractant for neutrophils which express IL8 receptors IL8RA and RB (IL8RA/B) on their membranes. Neutrophils interact with the damaged endothelium and initiate an inflammatory cascade at the site of injury. We have generated a novel translational targeted cell therapy for acute vascular injury using adenoviral vectors to overexpress IL8RA/B and green fluorescent protein (GFP) on the surface of endothelial cells (ECs) derived from human induced pluripotent stem cells (HiPS-IL8RA/B-ECs). We hypothesize that HiPS-IL8RA/B-ECs transfused intravenously into rats with balloon injury of the carotid artery will target to the injured site and compete with neutrophils, thus inhibiting inflammation and neointima formation. Young adult male Sprague-Dawley rats underwent balloon injury of the right carotid artery and received intravenous transfusion of saline vehicle, 1.5 × 10(6) HiPS-ECs, 1.5 × 10(6) HiPS-Null-ECs, or 1.5 × 10(6) HiPS-IL8RA/B-ECs immediately after endoluminal injury. Tissue distribution of HiPS-IL8RA/B-ECs was analyzed by a novel GFP DNA qPCR method. Cytokine and chemokine expression and leukocyte infiltration were measured in injured and uninjured arteries at 24 h postinjury by ELISA and immunohistochemistry, respectively. Neointimal, medial areas, and reendothelialization were measured 14 days postinjury. HiPS-IL8RA/B-ECs homed to injured arteries, inhibited inflammatory mediator expression and inflammatory cell infiltration, accelerated reendothelialization, and attenuated neointima formation after endoluminal injury while control HiPS-ECs and HiPS-Null-ECs did not. HiPS-IL8RA/B-ECs transfused into rats with endoluminal carotid artery injury target to the injured artery and provide a novel strategy to treat vascular injury.

    View details for DOI 10.1152/ajpheart.00587.2015

    View details for PubMedID 26801304

  • Nanoscale Patterning of Extracellular Matrix Alters Endothelial Function under Shear Stress NANO LETTERS Nakayama, K. H., Surya, V. N., Gole, M., Walker, T. W., Yang, W., Lai, E. S., Ostrowski, M. A., Fuller, G. G., Dunn, A. R., Huang, N. F. 2016; 16 (1): 410-419

    Abstract

    The role of nanotopographical extracellular matrix (ECM) cues in vascular endothelial cell (EC) organization and function is not well-understood, despite the composition of nano- to microscale fibrillar ECMs within blood vessels. Instead, the predominant modulator of EC organization and function is traditionally thought to be hemodynamic shear stress, in which uniform shear stress induces parallel-alignment of ECs with anti-inflammatory function, whereas disturbed flow induces a disorganized configuration with pro-inflammatory function. Since shear stress acts on ECs by applying a mechanical force concomitant with inducing spatial patterning of the cells, we sought to decouple the effects of shear stress using parallel-aligned nanofibrillar collagen films that induce parallel EC alignment prior to stimulation with disturbed flow resulting from spatial wall shear stress gradients. Using real time live-cell imaging, we tracked the alignment, migration trajectories, proliferation, and anti-inflammatory behavior of ECs when they were cultured on parallel-aligned or randomly oriented nanofibrillar films. Intriguingly, ECs cultured on aligned nanofibrillar films remained well-aligned and migrated predominantly along the direction of aligned nanofibrils, despite exposure to shear stress orthogonal to the direction of the aligned nanofibrils. Furthermore, in stark contrast to ECs cultured on randomly oriented films, ECs on aligned nanofibrillar films exposed to disturbed flow had significantly reduced inflammation and proliferation, while maintaining intact intercellular junctions. This work reveals fundamental insights into the importance of nanoscale ECM interactions in the maintenance of endothelial function. Importantly, it provides new insight into how ECs respond to opposing cues derived from nanotopography and mechanical shear force and has strong implications in the design of polymeric conduits and bioengineered tissues.

    View details for DOI 10.1021/acs.nanolett.5b04028

    View details for Web of Science ID 000368322700064

    View details for PubMedCentralID PMC4758680

  • Nanoscale Patterning of Extracellular Matrix Alters Endothelial Function under Shear Stress. Nano letters Nakayama, K. H., Surya, V. N., Gole, M., Walker, T. W., Yang, W., Lai, E. S., Ostrowski, M. A., Fuller, G. G., Dunn, A. R., Huang, N. F. 2016; 16 (1): 410–19

    Abstract

    The role of nanotopographical extracellular matrix (ECM) cues in vascular endothelial cell (EC) organization and function is not well-understood, despite the composition of nano- to microscale fibrillar ECMs within blood vessels. Instead, the predominant modulator of EC organization and function is traditionally thought to be hemodynamic shear stress, in which uniform shear stress induces parallel-alignment of ECs with anti-inflammatory function, whereas disturbed flow induces a disorganized configuration with pro-inflammatory function. Since shear stress acts on ECs by applying a mechanical force concomitant with inducing spatial patterning of the cells, we sought to decouple the effects of shear stress using parallel-aligned nanofibrillar collagen films that induce parallel EC alignment prior to stimulation with disturbed flow resulting from spatial wall shear stress gradients. Using real time live-cell imaging, we tracked the alignment, migration trajectories, proliferation, and anti-inflammatory behavior of ECs when they were cultured on parallel-aligned or randomly oriented nanofibrillar films. Intriguingly, ECs cultured on aligned nanofibrillar films remained well-aligned and migrated predominantly along the direction of aligned nanofibrils, despite exposure to shear stress orthogonal to the direction of the aligned nanofibrils. Furthermore, in stark contrast to ECs cultured on randomly oriented films, ECs on aligned nanofibrillar films exposed to disturbed flow had significantly reduced inflammation and proliferation, while maintaining intact intercellular junctions. This work reveals fundamental insights into the importance of nanoscale ECM interactions in the maintenance of endothelial function. Importantly, it provides new insight into how ECs respond to opposing cues derived from nanotopography and mechanical shear force and has strong implications in the design of polymeric conduits and bioengineered tissues.

    View details for PubMedID 26670737

  • Aligned-Braided Nanofibrillar Scaffold with Endothelial Cells Enhances Arteriogenesis. ACS nano Nakayama, K. H., Hong, G., Lee, J. C., Patel, J., Edwards, B., Zaitseva, T. S., Paukshto, M. V., Dai, H., Cooke, J. P., Woo, Y. J., Huang, N. F. 2015; 9 (7): 6900-6908

    Abstract

    The objective of this study was to enhance the angiogenic capacity of endothelial cells (ECs) using nanoscale signaling cues from aligned nanofibrillar scaffolds in the setting of tissue ischemia. Thread-like nanofibrillar scaffolds with porous structure were fabricated from aligned-braided membranes generated under shear from liquid crystal collagen solution. Human ECs showed greater outgrowth from aligned scaffolds than from nonpatterned scaffolds. Integrin α1 was in part responsible for the enhanced cellular outgrowth on aligned nanofibrillar scaffolds, as the effect was abrogated by integrin α1 inhibition. To test the efficacy of EC-seeded aligned nanofibrillar scaffolds in improving neovascularization in vivo, the ischemic limbs of mice were treated with EC-seeded aligned nanofibrillar scaffold; EC-seeded nonpatterned scaffold; ECs in saline; aligned nanofibrillar scaffold alone; or no treatment. After 14 days, laser Doppler blood spectroscopy demonstrated significant improvement in blood perfusion recovery when treated with EC-seeded aligned nanofibrillar scaffolds, in comparison to ECs in saline or no treatment. In ischemic hindlimbs treated with scaffolds seeded with human ECs derived from induced pluripotent stem cells (iPSC-ECs), single-walled carbon nanotube (SWNT) fluorophores were systemically delivered to quantify microvascular density after 28 days. Near infrared-II (NIR-II, 1000-1700 nm) imaging of SWNT fluorophores demonstrated that iPSC-EC-seeded aligned scaffolds group showed significantly higher microvascular density than the saline or cells groups. These data suggest that treatment with EC-seeded aligned nanofibrillar scaffolds improved blood perfusion and arteriogenesis, when compared to treatment with cells alone or scaffold alone, and have important implications in the design of therapeutic cell delivery strategies.

    View details for DOI 10.1021/acsnano.5b00545

    View details for PubMedID 26061869

  • Bilayered vascular graft derived from human induced pluripotent stem cells with biomimetic structure and function REGENERATIVE MEDICINE Nakayama, K. H., Joshi, P. A., Lai, E. S., Gujar, P., Joubert, L., Chen, B., Huang, N. F. 2015; 10 (6): 745-755

    Abstract

    We developed an aligned bi-layered vascular graft derived from human induced pluripotent stem cells (iPSCs) that recapitulates the cellular composition, orientation, and anti-inflammatory function of blood vessels.The luminal layer consisted of longitudinal-aligned nanofibrillar collagen containing primary endothelial cells (ECs) or iPSC-derived ECs (iPSC-ECs). The outer layer contained circumferentially oriented nanofibrillar collagen with primary smooth muscle cells (SMCs) or iPSC-derived SMCs(iPSC-SMCs).On the aligned scaffolds, cells organized F-actin assembly within 8º from the direction of nanofibrils. When compared to randomly-oriented scaffolds, EC-seeded aligned scaffolds had significant reduced inflammatory response, based on adhesivity to monocytes.This study highlights the importance of anisotropic scaffolds in directing cell form and function, and has therapeutic significance as physiologically relevant blood vessels.

    View details for DOI 10.2217/rme.15.45

    View details for Web of Science ID 000364574000005

    View details for PubMedID 26440211

  • Near-infrared II fluorescence for imaging hindlimb vessel regeneration with dynamic tissue perfusion measurement. Circulation. Cardiovascular imaging Hong, G., Lee, J. C., Jha, A., Diao, S., Nakayama, K. H., Hou, L., Doyle, T. C., Robinson, J. T., Antaris, A. L., Dai, H., Cooke, J. P., Huang, N. F. 2014; 7 (3): 517-525

    Abstract

    Real-time vascular imaging that provides both anatomic and hemodynamic information could greatly facilitate the diagnosis of vascular diseases and provide accurate assessment of therapeutic effects. Here, we have developed a novel fluorescence-based all-optical method, named near-infrared II (NIR-II) fluorescence imaging, to image murine hindlimb vasculature and blood flow in an experimental model of peripheral arterial disease, by exploiting fluorescence in the NIR-II region (1000-1400 nm) of photon wavelengths.Because of the reduced photon scattering of NIR-II fluorescence compared with traditional NIR fluorescence imaging and thus much deeper penetration depth into the body, we demonstrated that the mouse hindlimb vasculature could be imaged with higher spatial resolution than in vivo microscopic computed tomography. Furthermore, imaging during 26 days revealed a significant increase in hindlimb microvascular density in response to experimentally induced ischemia within the first 8 days of the surgery (P<0.005), which was confirmed by histological analysis of microvascular density. Moreover, the tissue perfusion in the ischemic hindlimb could be quantitatively measured by the dynamic NIR-II method, revealing the temporal kinetics of blood flow recovery that resembled microbead-based blood flowmetry and laser Doppler blood spectroscopy.The penetration depth of millimeters, high spatial resolution, and fast acquisition rate of NIR-II imaging make it a useful imaging tool for murine models of vascular disease.

    View details for DOI 10.1161/CIRCIMAGING.113.000305

    View details for PubMedID 24657826

  • Role of extracellular matrix signaling cues in modulating cell fate commitment for cardiovascular tissue engineering. Advanced healthcare materials Nakayama, K. H., Hou, L., Huang, N. F. 2014; 3 (5): 628-641

    Abstract

    It is generally agreed that engineered cardiovascular tissues require cellular interactions with the local milieu. Within the microenvironment, the extracellular matrix (ECM) is an important support structure that provides dynamic signaling cues in part through its chemical, physical, and mechanical properties. In response to ECM factors, cells activate biochemical and mechanotransduction pathways that modulate their survival, growth, migration, differentiation, and function. This Review describes the role of ECM chemical composition, spatial patterning, and mechanical stimulation in the specification of cardiovascular lineages, with a focus on stem cell differentiation, direct transdifferentiation, and endothelial-to-mesenchymal transition. The translational application of ECMs will be discussed in the context of cardiovascular tissue engineering and regenerative medicine.

    View details for DOI 10.1002/adhm.201300620

    View details for PubMedID 24443420

  • Multi-cellular interactions sustain long-term contractility of human pluripotent stem cell-derived cardiomyocytes. American journal of translational research Burridge, P. W., Metzler, S. A., Nakayama, K. H., Abilez, O. J., Simmons, C. S., Bruce, M. A., Matsuura, Y., Kim, P., Wu, J. C., Butte, M., Huang, N. F., Yang, P. C. 2014; 6 (6): 724-735

    Abstract

    Therapeutic delivery of cardiomyocytes derived from human pluripotent stem cells (hPSC-CMs) represents a novel clinical approach to regenerate the injured myocardium. However, poor survival and contractility of these cells are a significant bottleneck to their clinical use. To better understand the role of cell-cell communication in enhancing the phenotype and contractile properties of hPSC-CMs, we developed a three-dimensional (3D) hydrogel composed of hPSC-CMs, human pluripotent stem cell-derived endothelial cells (hPSC-ECs), and/or human amniotic mesenchymal stem cells (hAMSCs). The objective of this study was to examine the role of multi-cellular interactions among hPSC-ECs and hAMSCs on the survival and long-term contractile phenotype of hPSC-CMs in a 3D hydrogel. Quantification of spontaneous contractility of hPSC-CMs in tri-culture demonstrated a 6-fold increase in the area of contractile motion after 6 weeks with characteristic rhythmic contraction frequency, when compared to hPSC-CMs alone (P < 0.05). This finding was supported by a statistically significant increase in cardiac troponin T protein expression in the tri-culture hydrogel construct at 6 weeks, when compared to hPSC-CMs alone (P < 0.001). The sustained hPSC-CM survival and contractility in tri-culture was associated with a significant upregulation in the gene expression of L-type Ca(2+) ion channel, Cav1.2, and the inward-rectifier potassium channel, Kir2.1 (P < 0.05), suggesting a role of ion channels in mediating these processes. These findings demonstrate that multi-cellular interactions modulate hPSC-CM phenotype, function, and survival, and they will have important implications in engineering cardiac tissues for treatment of cardiovascular diseases.

    View details for PubMedID 25628783

  • Tissue specificity of decellularized rhesus monkey kidney and lung scaffolds. PloS one Nakayama, K. H., Lee, C. C., Batchelder, C. A., Tarantal, A. F. 2013; 8 (5)

    Abstract

    Initial steps in establishing an optimal strategy for functional bioengineered tissues is generation of three-dimensional constructs containing cells with the appropriate organization and phenotype. To effectively utilize rhesus monkey decellularized kidney scaffolds, these studies evaluated two key parameters: (1) residual scaffold components after decellularization including proteomics analysis, and (2) the use of undifferentiated human embryonic stem cells (hESCs) for recellularization in order to explore cellular differentiation in a tissue-specific manner. Sections of kidney and lung were selected for a comparative evaluation because of their similar pattern of organogenesis. Proteomics analysis revealed the presence of growth factors and antimicrobial proteins as well as stress proteins and complement components. Immunohistochemistry of recellularized kidney scaffolds showed the generation of Cytokeratin+ epithelial tubule phenotypes throughout the scaffold that demonstrated a statistically significant increase in expression of kidney-associated genes compared to baseline hESC gene expression. Recellularization of lung scaffolds showed that cells lined the alveolar spaces and demonstrated statistically significant upregulation of key lung-associated genes. However, overall expression of kidney and lung-associated markers was not statistically different when the kidney and lung recellularized scaffolds were compared. These results suggest that decellularized scaffolds have an intrinsic spatial ability to influence hESC differentiation by physically shaping cells into tissue-appropriate structures and phenotypes, and that additional approaches may be needed to ensure consistent recellularization throughout the matrix.

    View details for DOI 10.1371/journal.pone.0064134

    View details for PubMedID 23717553

  • Renal Tissue Engineering with Decellularized Rhesus Monkey Kidneys: Age-Related Differences TISSUE ENGINEERING PART A Nakayama, K. H., Batchelder, C. A., Lee, C. I., Tarantal, A. F. 2011; 17 (23-24): 2891-2901

    Abstract

    New therapies for severely damaged kidneys are needed due to limited regenerative capacity and organ donor shortages. The goal of this study was to repopulate decellularized kidney sections in vitro and to determine the impact of donor age on recellularization. This was addressed by generating decellularized kidney scaffolds from fetal, juvenile, and adult rhesus monkey kidney sections using a procedure that removes cellular components while preserving the structural and functional properties of the native extracellular matrix (ECM). Kidney scaffolds were recellularized using explants from different age groups (fetal, juvenile, adult) and fetal renal cell fractions. Results showed vimentin+ cytokeratin+ calbindin+ cell infiltration and organization around the scaffold ECM. The extent of cellular repopulation was greatest with scaffolds from the youngest donors, and with seeding of mixed fetal renal aggregates that formed tubular structures within the kidney scaffolds. These findings suggest that decellularized kidney sections from different age groups can be effectively repopulated with donor cells and the age of the donor is a critical factor in repopulation efficiency.

    View details for DOI 10.1089/ten.tea.2010.0714

    View details for Web of Science ID 000298077900001

    View details for PubMedID 21902603

  • Use of large animal and nonhuman primate models for cell therapy and tissue engineering Tissue Engineering in Regenerative Medicine Tarantal AF, Nakayama KH 2011: 393-413
  • Decellularized Rhesus Monkey Kidney as a Three-Dimensional Scaffold for Renal Tissue Engineering TISSUE ENGINEERING PART A Nakayama, K. H., Batchelder, C. A., Lee, C. I., Tarantal, A. F. 2010; 16 (7): 2207-2216

    Abstract

    The goal of this study was the production of a decellularized kidney scaffold with structural, mechanical, and physiological properties necessary for engineering basic renal structures in vitro. Fetal, infant, juvenile, and adult rhesus monkey kidney sections were treated with either 1% (v/v) sodium dodecyl sulfate or Triton X-100 followed by quantitative and qualitative analysis. Comparison of decellularization agents and incubation temperatures demonstrated sodium dodecyl sulfate at 4 degrees C to be most effective in preserving the native architecture. Hematoxylin and eosin staining confirmed the removal of cellular material, and immunohistochemistry demonstrated preservation of native expression patterns of extracellular matrix proteins, including heparan sulfate proteoglycan, fibronectin, collagen types I and IV, and laminin. Biomechanical testing revealed a decrease in the compressive modulus of decellularized compared to fresh kidneys. Layering of fetal kidney explants on age-matched decellularized kidney scaffolds demonstrated the capacity of the scaffold to support Pax2+/vimentin+ cell attachment and migration to recellularize the scaffold. These findings demonstrate that decellularized kidney sections retain critical structural and functional properties necessary for use as a three-dimensional scaffold and promote cellular repopulation. Further, this study provides the initial steps in developing new regenerative medicine strategies for renal tissue engineering and repair.

    View details for DOI 10.1089/ten.tea.2009.0602

    View details for Web of Science ID 000279455500010

    View details for PubMedID 20156112