Mesenchymal stromal cell treatment of donor kidneys during ex vivo normothermic machine perfusion: A porcine renal autotransplantation study
Normothermic machine perfusion (NMP) of injured kidneys offers the opportunity for interventions to metabolically active organs prior to transplantation. Mesenchymal stromal cells (MSCs) can exert regenerative and anti‐inflammatory effects in ischemia‐reperfusion injury. The aims of this study were...
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| Veröffentlicht in: | American journal of transplantation 2021-07, Vol.21 (7), p.2348-2359 |
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| creator | Lohmann, Stine Pool, Merel B. F. Rozenberg, Kaithlyn M. Keller, Anna K. Moers, Cyril Møldrup, Ulla Møller, Bjarne K. Lignell, Stina J. M. Krag, Søren Sierra‐Parraga, Jesus M. Lo Faro, Maria L. Hunter, James Hoogduijn, Martin J. Baan, Carla C. Leuvenink, Henri G. D. Ploeg, Rutger J. Eijken, Marco Jespersen, Bente |
| description | Normothermic machine perfusion (NMP) of injured kidneys offers the opportunity for interventions to metabolically active organs prior to transplantation. Mesenchymal stromal cells (MSCs) can exert regenerative and anti‐inflammatory effects in ischemia‐reperfusion injury. The aims of this study were to evaluate the safety and feasibility of MSC treatment of kidneys during NMP using a porcine autotransplantation model, and examine potential MSC treatment‐associated kidney improvements up to 14 days posttransplant. After 75 min of kidney warm ischemia, four experimental groups of n = 7 underwent 14 h of oxygenated hypothermic machine perfusion. In three groups this was followed by 240 min of NMP with infusion of vehicle, 10 million porcine, or 10 million human adipose‐derived MSCs. All kidneys were autotransplanted after contralateral nephrectomy. MSC treatment did not affect perfusion hemodynamics during NMP or cause adverse effects at reperfusion, with 100% animal survival. MSCs did not affect plasma creatinine, glomerular filtration rate, neutrophil gelatinase‐associated lipocalin concentrations or kidney damage assessed by histology during the 14 days, and MSCs retention was demonstrated in renal cortex. Infusing MSCs during ex vivo NMP of porcine kidneys was safe and feasible. Within the short posttransplant follow‐up period, no beneficial effects of ex vivo MSC therapy could be demonstrated.
This study shows that while intra‐arterial infusion of mesenchymal stromal cells (MSCs) during kidney normothermic machine perfusion does not affect perfusion hemodynamics, MSCs, albeit detectible in the renal cortex, do not affect plasma creatinine, glomerular filtration rate, neutrophil gelatinase‐associated lipocalin concentrations, or kidney damage assessed 14 days after transplant. |
| doi_str_mv | 10.1111/ajt.16473 |
| format | Article |
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This study shows that while intra‐arterial infusion of mesenchymal stromal cells (MSCs) during kidney normothermic machine perfusion does not affect perfusion hemodynamics, MSCs, albeit detectible in the renal cortex, do not affect plasma creatinine, glomerular filtration rate, neutrophil gelatinase‐associated lipocalin concentrations, or kidney damage assessed 14 days after transplant.</description><identifier>ISSN: 1600-6135</identifier><identifier>EISSN: 1600-6143</identifier><identifier>DOI: 10.1111/ajt.16473</identifier><identifier>PMID: 33382194</identifier><language>eng</language><publisher>United States: Elsevier Limited</publisher><subject>Animals ; basic (laboratory) research/science ; Creatinine ; donors and donation: donation after circulatory death (DCD) ; Gelatinase ; Glomerular filtration rate ; Hemodynamics ; Humans ; Inflammation ; Ischemia ; ischemia reperfusion injury (IRI) ; Kidney ; kidney transplantation/nephrology ; Kidney transplants ; Kidneys ; Leukocytes (neutrophilic) ; Lipocalin ; Mesenchymal Stem Cells ; Mesenchyme ; Nephrectomy ; organ perfusion and preservation ; Organ Preservation ; organ procurement and allocation ; Perfusion ; regenerative medicine ; Renal cortex ; Reperfusion ; stem cells ; Stromal cells ; Swine ; Transplantation ; Transplantation, Autologous</subject><ispartof>American journal of transplantation, 2021-07, Vol.21 (7), p.2348-2359</ispartof><rights>2021 The American Society of Transplantation and the American Society of Transplant Surgeons</rights><rights>2021 The American Society of Transplantation and the American Society of Transplant Surgeons.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4283-e5d7fa89b2bb8c265815aea98ac3341fef4ed484f7f29824a706231e0823d14c3</citedby><cites>FETCH-LOGICAL-c4283-e5d7fa89b2bb8c265815aea98ac3341fef4ed484f7f29824a706231e0823d14c3</cites><orcidid>0000-0001-7801-665X ; 0000-0002-3774-4471</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fajt.16473$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fajt.16473$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33382194$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lohmann, Stine</creatorcontrib><creatorcontrib>Pool, Merel B. F.</creatorcontrib><creatorcontrib>Rozenberg, Kaithlyn M.</creatorcontrib><creatorcontrib>Keller, Anna K.</creatorcontrib><creatorcontrib>Moers, Cyril</creatorcontrib><creatorcontrib>Møldrup, Ulla</creatorcontrib><creatorcontrib>Møller, Bjarne K.</creatorcontrib><creatorcontrib>Lignell, Stina J. M.</creatorcontrib><creatorcontrib>Krag, Søren</creatorcontrib><creatorcontrib>Sierra‐Parraga, Jesus M.</creatorcontrib><creatorcontrib>Lo Faro, Maria L.</creatorcontrib><creatorcontrib>Hunter, James</creatorcontrib><creatorcontrib>Hoogduijn, Martin J.</creatorcontrib><creatorcontrib>Baan, Carla C.</creatorcontrib><creatorcontrib>Leuvenink, Henri G. D.</creatorcontrib><creatorcontrib>Ploeg, Rutger J.</creatorcontrib><creatorcontrib>Eijken, Marco</creatorcontrib><creatorcontrib>Jespersen, Bente</creatorcontrib><title>Mesenchymal stromal cell treatment of donor kidneys during ex vivo normothermic machine perfusion: A porcine renal autotransplantation study</title><title>American journal of transplantation</title><addtitle>Am J Transplant</addtitle><description>Normothermic machine perfusion (NMP) of injured kidneys offers the opportunity for interventions to metabolically active organs prior to transplantation. Mesenchymal stromal cells (MSCs) can exert regenerative and anti‐inflammatory effects in ischemia‐reperfusion injury. The aims of this study were to evaluate the safety and feasibility of MSC treatment of kidneys during NMP using a porcine autotransplantation model, and examine potential MSC treatment‐associated kidney improvements up to 14 days posttransplant. After 75 min of kidney warm ischemia, four experimental groups of n = 7 underwent 14 h of oxygenated hypothermic machine perfusion. In three groups this was followed by 240 min of NMP with infusion of vehicle, 10 million porcine, or 10 million human adipose‐derived MSCs. All kidneys were autotransplanted after contralateral nephrectomy. MSC treatment did not affect perfusion hemodynamics during NMP or cause adverse effects at reperfusion, with 100% animal survival. MSCs did not affect plasma creatinine, glomerular filtration rate, neutrophil gelatinase‐associated lipocalin concentrations or kidney damage assessed by histology during the 14 days, and MSCs retention was demonstrated in renal cortex. Infusing MSCs during ex vivo NMP of porcine kidneys was safe and feasible. Within the short posttransplant follow‐up period, no beneficial effects of ex vivo MSC therapy could be demonstrated.
This study shows that while intra‐arterial infusion of mesenchymal stromal cells (MSCs) during kidney normothermic machine perfusion does not affect perfusion hemodynamics, MSCs, albeit detectible in the renal cortex, do not affect plasma creatinine, glomerular filtration rate, neutrophil gelatinase‐associated lipocalin concentrations, or kidney damage assessed 14 days after transplant.</description><subject>Animals</subject><subject>basic (laboratory) research/science</subject><subject>Creatinine</subject><subject>donors and donation: donation after circulatory death (DCD)</subject><subject>Gelatinase</subject><subject>Glomerular filtration rate</subject><subject>Hemodynamics</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Ischemia</subject><subject>ischemia reperfusion injury (IRI)</subject><subject>Kidney</subject><subject>kidney transplantation/nephrology</subject><subject>Kidney transplants</subject><subject>Kidneys</subject><subject>Leukocytes (neutrophilic)</subject><subject>Lipocalin</subject><subject>Mesenchymal Stem Cells</subject><subject>Mesenchyme</subject><subject>Nephrectomy</subject><subject>organ perfusion and preservation</subject><subject>Organ Preservation</subject><subject>organ procurement and allocation</subject><subject>Perfusion</subject><subject>regenerative medicine</subject><subject>Renal cortex</subject><subject>Reperfusion</subject><subject>stem cells</subject><subject>Stromal cells</subject><subject>Swine</subject><subject>Transplantation</subject><subject>Transplantation, Autologous</subject><issn>1600-6135</issn><issn>1600-6143</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc9OGzEQhy1UVFLogRdAlnqBQ8L6z-56uUVRaYuoegnnleMdE6e79tb2puw79KFxSMoBibnMyP70jUY_hM5JNiOpruUmzkjBS3aEJqTIsmlBOPvwOrP8BH0KYZNlpKSCfkQnjDFBScUn6N9PCGDVeuxki0P0btcVtC2OHmTswEbsNG6cdR7_No2FMeBm8MY-YnjCW7N1OH11Lq7Bd0bhTqq1sYB78HoIxtkbPMe982r36MEmvRyii17a0LfSRhkTlFYPzXiGjrVsA3w-9FP0cPt1ufg-vf_17cdifj9VnAo2hbwptRTViq5WQtEiFySXICshFWOcaNAcGi64LjWtBOWyzArKCGSCsoZwxU7R5d7be_dngBDrzoTd0dKCG0JNecl5kVdFntAvb9CNG3y6IlE5L4QgrGSJutpTyrsQPOi696aTfqxJVu8iqlNE9UtEib04GIdVB80r-T-TBFzvgb-mhfF9Uz2_W-6Vz8nynZk</recordid><startdate>202107</startdate><enddate>202107</enddate><creator>Lohmann, Stine</creator><creator>Pool, Merel B. 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D.</creatorcontrib><creatorcontrib>Ploeg, Rutger J.</creatorcontrib><creatorcontrib>Eijken, Marco</creatorcontrib><creatorcontrib>Jespersen, Bente</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lohmann, Stine</au><au>Pool, Merel B. F.</au><au>Rozenberg, Kaithlyn M.</au><au>Keller, Anna K.</au><au>Moers, Cyril</au><au>Møldrup, Ulla</au><au>Møller, Bjarne K.</au><au>Lignell, Stina J. M.</au><au>Krag, Søren</au><au>Sierra‐Parraga, Jesus M.</au><au>Lo Faro, Maria L.</au><au>Hunter, James</au><au>Hoogduijn, Martin J.</au><au>Baan, Carla C.</au><au>Leuvenink, Henri G. D.</au><au>Ploeg, Rutger J.</au><au>Eijken, Marco</au><au>Jespersen, Bente</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mesenchymal stromal cell treatment of donor kidneys during ex vivo normothermic machine perfusion: A porcine renal autotransplantation study</atitle><jtitle>American journal of transplantation</jtitle><addtitle>Am J Transplant</addtitle><date>2021-07</date><risdate>2021</risdate><volume>21</volume><issue>7</issue><spage>2348</spage><epage>2359</epage><pages>2348-2359</pages><issn>1600-6135</issn><eissn>1600-6143</eissn><abstract>Normothermic machine perfusion (NMP) of injured kidneys offers the opportunity for interventions to metabolically active organs prior to transplantation. Mesenchymal stromal cells (MSCs) can exert regenerative and anti‐inflammatory effects in ischemia‐reperfusion injury. The aims of this study were to evaluate the safety and feasibility of MSC treatment of kidneys during NMP using a porcine autotransplantation model, and examine potential MSC treatment‐associated kidney improvements up to 14 days posttransplant. After 75 min of kidney warm ischemia, four experimental groups of n = 7 underwent 14 h of oxygenated hypothermic machine perfusion. In three groups this was followed by 240 min of NMP with infusion of vehicle, 10 million porcine, or 10 million human adipose‐derived MSCs. All kidneys were autotransplanted after contralateral nephrectomy. MSC treatment did not affect perfusion hemodynamics during NMP or cause adverse effects at reperfusion, with 100% animal survival. MSCs did not affect plasma creatinine, glomerular filtration rate, neutrophil gelatinase‐associated lipocalin concentrations or kidney damage assessed by histology during the 14 days, and MSCs retention was demonstrated in renal cortex. Infusing MSCs during ex vivo NMP of porcine kidneys was safe and feasible. Within the short posttransplant follow‐up period, no beneficial effects of ex vivo MSC therapy could be demonstrated.
This study shows that while intra‐arterial infusion of mesenchymal stromal cells (MSCs) during kidney normothermic machine perfusion does not affect perfusion hemodynamics, MSCs, albeit detectible in the renal cortex, do not affect plasma creatinine, glomerular filtration rate, neutrophil gelatinase‐associated lipocalin concentrations, or kidney damage assessed 14 days after transplant.</abstract><cop>United States</cop><pub>Elsevier Limited</pub><pmid>33382194</pmid><doi>10.1111/ajt.16473</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-7801-665X</orcidid><orcidid>https://orcid.org/0000-0002-3774-4471</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals basic (laboratory) research/science Creatinine donors and donation: donation after circulatory death (DCD) Gelatinase Glomerular filtration rate Hemodynamics Humans Inflammation Ischemia ischemia reperfusion injury (IRI) Kidney kidney transplantation/nephrology Kidney transplants Kidneys Leukocytes (neutrophilic) Lipocalin Mesenchymal Stem Cells Mesenchyme Nephrectomy organ perfusion and preservation Organ Preservation organ procurement and allocation Perfusion regenerative medicine Renal cortex Reperfusion stem cells Stromal cells Swine Transplantation Transplantation, Autologous |
| title | Mesenchymal stromal cell treatment of donor kidneys during ex vivo normothermic machine perfusion: A porcine renal autotransplantation study |
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