Proteomic Profiling Reveals the Ambivalent Character of the Mesenchymal Stem Cell Secretome: Assessing the Effect of Preconditioned Media on Isolated Human Islets.

Abstract:

:Previous studies in rodents have indicated that function and survival of transplanted islets can be substantially improved by mesenchymal stem cells (MSC). The few human islet studies to date have confirmed these findings but have not determined whether physical contact between MSC and islets is required or whether the benefit to islets results from MSC-secreted proteins. This study aimed to investigate the protective capacity of MSC-preconditioned media for human islets. MSC were cultured for 2 or 5 days in normoxia or hypoxia before harvesting the cell-depleted media for human islet culture in normoxia or hypoxia for 6-8 or 3-4 days, respectively. To characterize MSC-preconditioned media, proteomic secretome profiling was performed to identify angiogenesis- and inflammation-related proteins. A protective effect of MSC-preconditioned media on survival and in vitro function of hypoxic human islets was observed irrespective of the atmosphere used for MSC preconditioning. Islet morphology changed markedly when media from hypoxic MSC were used for culture. However, PDX-1 and insulin gene expression did not confirm a change in the genetic phenotype of these islets. Proteomic profiling of preconditioned media revealed the heterogenicity of the secretome comprising angiogenic and antiapoptotic as well as angiostatic or proinflammatory mediators released at an identical pattern regardless whether MSC had been cultured in normoxic or hypoxic atmosphere. These findings do not allow a clear discrimination between normoxia and hypoxia as stimulus for protective MSC capabilities but indicate an ambivalent character of the MSC angiogenesis- and inflammation-related secretome. Nevertheless, culture of human islets in acellular MSC-preconditioned media resulted in improved morphological and functional islet integrity suggesting a disbalance in favor of protective factors. Further approaches should aim to eliminate potentially detrimental factors to enable the production of advanced clinical grade islet culture media with higher protective qualities.

journal_name

Cell Transplant

journal_title

Cell transplantation

authors

Brandhorst H,Brandhorst D,Abraham A,Acreman S,Schive SW,Scholz H,Johnson PRV

doi

10.1177/0963689720952332

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

963689720952332

eissn

0963-6897

issn

1555-3892

journal_volume

29

pub_type

杂志文章
  • 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase Suppresses Neuronal Apoptosis by Increasing Glycolysis and "cyclin-dependent kinase 1-Mediated Phosphorylation of p27 After Traumatic Spinal Cord Injury in Rats.

    abstract::Apoptosis is a vital pathological factor that accounts for the poor prognosis of traumatic spinal cord injury (t-SCI). The 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) is a critical regulator for energy metabolism and proven to have antiapoptotic effects. This study aimed to investigate the neuroprote...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.1177/0963689720950226

    authors: Gao L,Wang C,Qin B,Li T,Xu W,Lenahan C,Ying G,Li J,Zhao T,Zhu Y,Chen G

    更新日期:2020-01-01 00:00:00

  • A molecular basis of cryopreservation failure and its modulation to improve cell survival.

    abstract::The requirement for more effective cryopreservation (CP) methodologies in support of the emerging fields of cell bioprocessing and cell therapy is now critical. Current CP strategies appropriately focus on minimizing the damaging actions of physicochemical stressors and membrane disruption associated with extra- and i...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:

    authors: Baust JM,Vogel MJ,Van Buskirk R,Baust JG

    更新日期:2001-01-01 00:00:00

  • Enhanced Neurogenesis and Collaterogenesis by Sodium Danshensu Treatment After Focal Cerebral Ischemia in Mice.

    abstract::Ischemic stroke remains a serious threat to human life. There are limited effective therapies for the treatment of stroke. We have previously demonstrated that angiogenesis and neurogenesis in the brain play an important role in functional recovery following ischemic stroke. Recent studies indicate that increased arte...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.1177/0963689718771889

    authors: Wei ZZ,Chen D,Liu LP,Gu X,Zhong W,Zhang YB,Wang Y,Yu SP,Wei L

    更新日期:2018-04-01 00:00:00

  • Therapeutic effects of CTLA4Ig gene-transduced adipose tissue-derived mesenchymal stem cell transplantation on established autoimmune thyroiditis.

    abstract::This study aimed to identify the beneficial effects of adipose tissue-derived mesenchymal stem cells (ASCs) and ASCs that overexpress the CTLA4Ig gene (CTLA4Ig-ASCs) on established autoimmune thyroiditis and to examine changes in clinical chemistry parameters and the presence of humoral responses upon repeated long-te...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.3727/096368914X685122

    authors: Choi EW,Lee JM,Lee HW,Yang J,Youn HY

    更新日期:2015-01-01 00:00:00

  • The effects of digestion enzymes on islet viability and cellular composition.

    abstract::The choice of enzyme blend is critical for successful islet isolation. Islet yield, viability, integrity, and function are important factors that influence the outcome of islet transplantation. Liberase HI has been used as a standard enzyme for pancreas digestion and has successfully produced islets that reversed dia...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.3727/096368911X623826

    authors: Iglesias I,Valiente L,Shiang KD,Ichii H,Kandeel F,Al-Abdullah IH

    更新日期:2012-01-01 00:00:00

  • Intravenous transplantation of olfactory bulb ensheathing cells for a spinal cord hemisection injury rat model.

    abstract::Cellular transplantation strategies utilizing intraspinal or intrathecal olfactory ensheathing cells (OECs) have been reported as beneficial for spinal cord injury (SCI). However, there are many disadvantages of these methods, including additional trauma to the spinal cord parenchyma and technical challenges. Therefor...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.1177/0963689719883842

    authors: Zhang L,Zhuang X,Chen Y,Xia H

    更新日期:2019-12-01 00:00:00

  • Mechanical stress-induced orientation and ultrastructural change of smooth muscle cells cultured in three-dimensional collagen lattices.

    abstract::The effect of tensile stress on the orientation and phenotype of arterial smooth muscle cells (SMCs) cultured in three-dimensional (3D) type I collagen gels was morphologically investigated. Ring-shaped hybrid tissues were prepared by thermal gelation of a cold mixed solution of type I collagen and SMCs derived from b...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.1177/096368979400300605

    authors: Kanda K,Matsuda T

    更新日期:1994-11-01 00:00:00

  • Autologous G-CSF-mobilized peripheral blood CD34+ cell therapy for diabetic patients with chronic nonhealing ulcer.

    abstract::Recently, animal studies have demonstrated the efficacy of endothelial progenitor cell (EPC) therapy for diabetic wound healing. Based on these preclinical studies, we performed a prospective clinical trial phase I/IIa study of autologous G-CSF-mobilized peripheral blood (PB) CD34(+) cell transplantation for nonhealin...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.3727/096368912X658007

    authors: Tanaka R,Masuda H,Kato S,Imagawa K,Kanabuchi K,Nakashioya C,Yoshiba F,Fukui T,Ito R,Kobori M,Wada M,Asahara T,Miyasaka M

    更新日期:2014-02-01 00:00:00

  • In vitro expansion of human hepatocytes is restricted by telomere-dependent replicative aging.

    abstract::Currently, different techniques to expand human hepatocytes in vitro are being investigated to generate enough cells for liver-directed cell therapies. However, based on observations in fibroblasts and other cell types, telomere attrition limits the proliferative capacity of normal somatic cells. Therefore, we explore...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.3727/000000003771000138

    authors: Wege H,Chui MS,Le HT,Strom SC,Zern MA

    更新日期:2003-01-01 00:00:00

  • G-CSF stimulation and coronary reinfusion of mobilized circulating mononuclear proangiogenic cells in patients with chronic ischemic heart disease:five-year results of the TOPCARE-G-CSF trial.

    abstract::Prognosis of patients with heart failure remains poor despite improved conventional and interventional treatment regimens. The improvement of neovascularization and repair processes by administration of bone marrow-derived cells modestly improved the recovery after acute myocardial infarction. However, circulating pat...

    journal_title:Cell transplantation

    pub_type: 杂志文章,随机对照试验

    doi:10.3727/096368912X654957

    authors: Honold J,Fischer-Rasokat U,Lehmann R,Leistner DM,Seeger FH,Schachinger V,Martin H,Dimmeler S,Zeiher AM,Assmus B

    更新日期:2012-01-01 00:00:00

  • Effects of the Post-Spinal Cord Injury Microenvironment on the Differentiation Capacity of Human Neural Stem Cells Derived from Induced Pluripotent Stem Cells.

    abstract::Spinal cord injury (SCI) causes loss of neural functions below the level of the lesion due to interruption of spinal pathways and secondary neurodegenerative processes. The transplant of neural stem cells (NSCs) is a promising approach for the repair of SCI. Reprogramming of adult somatic cells into induced pluripoten...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.3727/096368916X691312

    authors: López-Serrano C,Torres-Espín A,Hernández J,Alvarez-Palomo AB,Requena J,Gasull X,Edel MJ,Navarro X

    更新日期:2016-10-01 00:00:00

  • Effect of Polydeoxyribonucleotide on Angiogenesis and Wound Healing in an In Vitro Model of Osteoarthritis.

    abstract::Osteoarthritis (OA) is degenerative disease, leading to pain and functional disability. It is reported that polydeoxyribonucleotide (PDRN) is a suitable therapy for OA. However, the therapeutic mechanisms of PDRN in OA are not fully understood. To investigate the effect of PDRN in an in vitro model of OA, interleukin ...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.1177/0963689718804130

    authors: Baek A,Kim Y,Lee JW,Lee SC,Cho SR

    更新日期:2018-11-01 00:00:00

  • Posttranscriptional mechanisms of glucocorticoid antiproliferative effects: glucocorticoids inhibit IL-6-induced proliferation of B9 hybridoma cells.

    abstract::Addition of rIL-6 to IL-6-dependent B9 cells starved for IL-6 for 16-20 h stimulated a vigorous proliferative response. Glucocorticoids (GCs), in a concentration-dependent manner, inhibited rIL-6-stimulated proliferation of B9 cells This inhibition was specific for the GCs, evident by the capacity of the GCs, dexameth...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:

    authors: Almawi WY,Tamim H

    更新日期:2001-03-01 00:00:00

  • Redifferentiation of in vitro expanded adult articular chondrocytes by combining the hanging-drop cultivation method with hypoxic environment.

    abstract::The main purpose of this work has been to establish a new culturing technique to improve the chondrogenic commitment of isolated adult human chondrocytes, with the aim of being used during cell-based therapies or tissue engineering strategies. By using a rather novel technique to generate scaffold-free three-dimension...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.3727/096368908786576499

    authors: Martinez I,Elvenes J,Olsen R,Bertheussen K,Johansen O

    更新日期:2008-01-01 00:00:00

  • Immunogenicity and immunomodulatory properties of umbilical cord lining mesenchymal stem cells.

    abstract::We here present an immunologic head-to-head comparison between human umbilical cord lining mesenchymal stem cells (clMSCs) and adult bone marrow MSCs (bmMSCs) from patients >65 years of age. clMSCs had significantly lower HLA class I expression, higher production of tolerogenic TGF-β and IL-10, and showed significantl...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.3727/096368910X536473

    authors: Deuse T,Stubbendorff M,Tang-Quan K,Phillips N,Kay MA,Eiermann T,Phan TT,Volk HD,Reichenspurner H,Robbins RC,Schrepfer S

    更新日期:2011-01-01 00:00:00

  • End-stage organ failure: will regenerative medicine keep its promise?

    abstract::End-stage organ failure is a major cause of death worldwide that can occur in patients of all ages and transplantation is the current standard of care for chronic end-stage disease of many organs. Despite the success of organ transplantation, it is becoming clear that there will never be enough organs made available t...

    journal_title:Cell transplantation

    pub_type: 历史文章,杂志文章

    doi:10.3727/000000006783982340

    authors: Triolo F,Gridelli B

    更新日期:2006-01-01 00:00:00

  • Paracrine effects of mesenchymal stem cells induce senescence and differentiation of glioblastoma stem-like cells.

    abstract::Glioblastoma multiforme (GBM) displays high resistance to radiation and chemotherapy, due to the presence of a fraction of GBM stem-like cells (GSLCs), which are thus representing the target for GBM elimination. Since mesenchymal stem cells (MSCs) display high tumor tropism, we examined possible antitumor effects of t...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.3727/096368915X687787

    authors: Kološa K,Motaln H,Herold-Mende C,Koršič M,Lah TT

    更新日期:2015-01-01 00:00:00

  • Plasma Transfusion Promoted Reprogramming CD4+ T Lymphocytes Immune Response in Severe Sepsis Mice Model Through Modulating the Exosome Protein Galectin 9.

    abstract::Sepsis is a life-threatening disease that results in excessive stimulation of the host's immune cells. In the animal study, the purpose was to investigate the roles of fresh frozen plasma (FFP) transfusion in shaping the CD4+ T lymphocytes immune response through modulating the secreted exosome protein Galectin-9 in m...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.1177/0963689720947347

    authors: Zhang L,Zhang JP,Liu Y,Wang H,Cheng Y,Wang JH,Zhang WJ,Li ZZ,Guo JR

    更新日期:2020-01-01 00:00:00

  • Human neural stem cells overexpressing choline acetyltransferase restore cognitive function of kainic acid-induced learning and memory deficit animals.

    abstract::Alzheimer disease (AD) is a progressive neurodegenerative disease, which is characterized by loss of memory and cognitive function. In AD patients dysfunction of the cholinergic system is the main cause of cognitive disorders, and decreased activity of choline acetyltransferase (ChAT), an enzyme responsible for acety...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.3727/096368911X586765

    authors: Park D,Joo SS,Kim TK,Lee SH,Kang H,Lee HJ,Lim I,Matsuo A,Tooyama I,Kim YB,Kim SU

    更新日期:2012-01-01 00:00:00

  • Allogeneic versus xenogeneic immune reaction to bioengineered skin grafts.

    abstract::There are conflicting reports on the survival and immune reaction to allografts and xenografts of cultured skin substitutes (CSS). In this study, we investigated the allogeneic and xenogeneic responses to CSS of human keratinocytes and genetically engineered CSS expressing keratinocyte growth factor (KGF) that forms a...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.3727/000000004783983594

    authors: Erdag G,Morgan JR

    更新日期:2004-01-01 00:00:00

  • Effect of a new immunosuppressive agent, FTY720, on survival of islet allografts.

    abstract::A newly developed immunosuppressant, FTY720, has a unique mechanism that is quite different from those of conventional immunosuppressants, and is presumed to be mediated through decreases in the number of peripheral lymphocytes, especially helper T cells. This study was performed to ascertain whether this innovative d...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.1016/s0963-6897(98)00021-9

    authors: Yamasaki T,Inoue K,Hayashi H,Gu Y,Setoyama H,Ida J,Cui W,Kawakami Y,Kogire M,Imamura M

    更新日期:1998-07-01 00:00:00

  • Single-cell suspensions of cultured human keratinocytes in fibrin-glue reconstitute the epidermis.

    abstract::To overcome common disadvantages of standard cultured epidermal sheet grafts (CEG) we have developed a new technique of transplanting cultured human keratinocytes suspended as single cells in a fibrin-glue matrix (Keratinocyte-fibrin-glue suspension-KFGS). In an athymic mouse model with reproducible standardized full ...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.1016/s0963-6897(98)00005-0

    authors: Horch RE,Bannasch H,Kopp J,Andree C,Stark GB

    更新日期:1998-05-01 00:00:00

  • Beneficial effect of the nonpeptidyl low molecular weight radical scavenger IAC on cultured human islet function.

    abstract::We examined a possible protective effect of the nonpeptidyl low molecular weight radical scavenger IAC [bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decanedioate di-hydrochloride] on isolated human islet cells against isolation and culture oxidative stress. Islets isolated from pancreases of nondiabetic multiorgan ...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.3727/096368908787236639

    authors: Mancarella R,Del Guerra S,Masini M,Bugliani M,Valgimigli L,Pedulli GF,Paolini M,Canistro D,Armando A,Soleti A,Filipponi F,Mosca F,Boggi U,Del Prato S,Marchetti P,Lupi R

    更新日期:2008-01-01 00:00:00

  • Mesenchymal stem cells protective effect in adriamycin model of nephropathy.

    abstract::Mesenchymal stem cells (MSCs) may be of value in regeneration of renal tissue after damage; however, lack of biological knowledge and variability of results in animal models limit their utilization. We studied the effects of MSCs on podocytes in vitro and in vivo utilizing adriamycin (ADR) as a model of renal toxicity...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.3727/096368908787236567

    authors: Magnasco A,Corselli M,Bertelli R,Ibatici A,Peresi M,Gaggero G,Cappiello V,Chiavarina B,Mattioli G,Gusmano R,Ravetti JL,Frassoni F,Ghiggeri GM

    更新日期:2008-01-01 00:00:00

  • Antisense RNA sequences modulating the ataxin-1 message: molecular model of gene therapy for spinocerebellar ataxia type 1, a dominant-acting unstable trinucleotide repeat disease.

    abstract::Spinocerebellar ataxia type 1 (SCA1) is a dominant inherited disease caused by expanded trinucleotide repeats resulting in an increased polyglutamine tract in the gene product. As a potential therapeutic approach for SCA1, we tested antisense RNAs targeting two regions of the ataxin-1 message. Single-stranded regions ...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.3727/096368908786516729

    authors: Gao Y,Zu T,Low WC,Orr HT,McIvor RS

    更新日期:2008-01-01 00:00:00

  • Disproportionate hyperproinsulinemia, beta-cell restricted prohormone convertase 2 deficiency, and cell cycle inhibitors expression by human islets transplanted into athymic nude mice: insights into nonimmune-mediated mechanisms of delayed islet graft fai

    abstract::To learn more about nonimmune-mediated islet graft failure, we transplanted different preparations (preps) of isolated human islets under the kidney capsule of streptozotocin (STZ)-diabetic nude mice. One month after the implantation of 1,000 or 2,000 islets, grafts were harvested for morphological, immunohistochemica...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.3727/096368908787648137

    authors: Davalli AM,Perego L,Bertuzzi F,Finzi G,La Rosa S,Blau A,Placidi C,Nano R,Gregorini L,Perego C,Capella C,Folli F

    更新日期:2008-01-01 00:00:00

  • Development and Characterization of Human Cerebral Organoids: An Optimized Protocol.

    abstract::Studies of human neurodevelopmental disorders and stem cell-based regenerative transplants have been hampered by the lack of a model of the developing human brain. Stem cell-derived neurons suffer major limitations, including the ability to recapitulate the 3-dimensional architecture of a brain tissue and the represen...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.1177/0963689717752946

    authors: Yakoub AM,Sadek M

    更新日期:2018-03-01 00:00:00

  • Time-dependent effects on coronary remodeling and epicardial conductance after intracoronary injection of enriched hematopoietic bone marrow stem cells in patients with previous myocardial infarction.

    abstract::Bone marrow (BM) cells may interact with coronary endothelium and modulate coronary atherosclerosis. We investigated the time course of coronary luminal loss and changes in conductance after intracoronary injection of enriched hematopoietic BM stem cells in patients with previous myocardial infarction (MI). Among 24 p...

    journal_title:Cell transplantation

    pub_type: 杂志文章,随机对照试验

    doi:10.3727/096368907783338244

    authors: Vanderheyden M,Vercauteren S,Mansour S,Delrue L,Vandekerckhove B,Heyndrickx GR,Van Haute I,De Bruyne B,Timmermans F,Wijns W,Bartunek J

    更新日期:2007-01-01 00:00:00

  • Human Keratinocytes Adopt Neuronal Fates After In Utero Transplantation in the Developing Rat Brain.

    abstract::Human skin contains keratinocytes in the epidermis. Such cells share their ectodermal origin with the central nervous system (CNS). Recent studies have demonstrated that terminally differentiated somatic cells can adopt a pluripotent state, or can directly convert its phenotype to neurons, after ectopic expression of ...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.1177/0963689720978219

    authors: Tenorio-Mina A,Cortés D,Esquivel-Estudillo J,López-Ornelas A,Cabrera-Wrooman A,Lara-Rodarte R,Escobedo-Avila I,Vargas-Romero F,Toledo-Hernández D,Estudillo E,Acevedo-Fernández JJ,Tapia JS,Velasco I

    更新日期:2021-01-01 00:00:00

  • Enhanced functional maturation of fetal porcine hepatocytes in three-dimensional poly-L-lactic acid scaffolds: a culture condition suitable for engineered liver tissues in large-scale animal studies.

    abstract::To engineer liver tissues with a clinically significant size, in vivo evaluation of performance using large-scale animal studies are necessary before proceeding to human clinical trials. As pigs are the most suitable candidates, the development of culture conditions suitable for porcine hepatocyte progenitors is very ...

    journal_title:Cell transplantation

    pub_type: 杂志文章

    doi:10.3727/000000006783981486

    authors: Huang H,Hanada S,Kojima N,Sakai Y

    更新日期:2006-01-01 00:00:00