Improved Mobilization of Exogenous Mesenchymal Stem Cells to Bone for Fracture Healing and Sex Difference
Mesenchymal stem cell (MSC) transplantation has been tested in animal and clinical fracture studies. We have developed a bone‐seeking compound, LLP2A‐Alendronate (LLP2A‐Ale) that augments MSC homing to bone. The purpose of this study was to determine whether treatment with LLP2A‐Ale or a combination...
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| Veröffentlicht in: | Stem cells (Dayton, Ohio) Ohio), 2016-10, Vol.34 (10), p.2587-2600 |
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| creator | Yao, Wei Lay, Yu‐An Evan Kot, Alexander Liu, Ruiwu Zhang, Hongliang Chen, Haiyan Lam, Kit Lane, Nancy E. |
| description | Mesenchymal stem cell (MSC) transplantation has been tested in animal and clinical fracture studies. We have developed a bone‐seeking compound, LLP2A‐Alendronate (LLP2A‐Ale) that augments MSC homing to bone. The purpose of this study was to determine whether treatment with LLP2A‐Ale or a combination of LLP2A‐Ale and MSCs would accelerate bone healing in a mouse closed fracture model and if the effects are sex dependent. A right mid‐femur fracture was induced in two‐month‐old osterix‐mCherry (Osx‐mCherry) male and female reporter mice. The mice were subsequently treated with placebo, LLP2A‐Ale (500 μg/kg, IV), MSCs derived from wild‐type female Osx‐mCherry adipose tissue (ADSC, 3 x 105, IV) or ADSC + LLP2A‐Ale.
In phosphate buffered saline‐treated mice, females had higher systemic and surface‐based bone formation than males. However, male mice formed a larger callus and had higher volumetric bone mineral density and bone strength than females. LLP2A‐Ale treatment increased exogenous MSC homing to the fracture gaps, enhanced incorporation of these cells into callus formation, and stimulated endochondral bone formation. Additionally, higher engraftment of exogenous MSCs in fracture gaps seemed to contribute to overall fracture healing and improved bone strength. These effects were sex‐independent.
There was a sex‐difference in the rate of fracture healing. ADSC and LLP2A‐Ale combination treatment was superior to on callus formation, which was independent of sex. Increased mobilization of exogenous MSCs to fracture sites accelerated endochondral bone formation and enhanced bone tissue regeneration. Stem Cells 2016;34:2587–2600 |
| doi_str_mv | 10.1002/stem.2433 |
| format | Article |
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In phosphate buffered saline‐treated mice, females had higher systemic and surface‐based bone formation than males. However, male mice formed a larger callus and had higher volumetric bone mineral density and bone strength than females. LLP2A‐Ale treatment increased exogenous MSC homing to the fracture gaps, enhanced incorporation of these cells into callus formation, and stimulated endochondral bone formation. Additionally, higher engraftment of exogenous MSCs in fracture gaps seemed to contribute to overall fracture healing and improved bone strength. These effects were sex‐independent.
There was a sex‐difference in the rate of fracture healing. ADSC and LLP2A‐Ale combination treatment was superior to on callus formation, which was independent of sex. Increased mobilization of exogenous MSCs to fracture sites accelerated endochondral bone formation and enhanced bone tissue regeneration. Stem Cells 2016;34:2587–2600</description><identifier>ISSN: 1066-5099</identifier><identifier>EISSN: 1549-4918</identifier><identifier>DOI: 10.1002/stem.2433</identifier><identifier>PMID: 27334693</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Adipose Tissue - cytology ; Adipose‐derived stromal cells ; Alendronate - pharmacology ; Angiogenesis Osteogenesis ; Animals ; Bone Density - drug effects ; Bone‐targeted ; Bony Callus - pathology ; Dipeptides - pharmacology ; Female ; Femoral Fractures - pathology ; Femoral Fractures - physiopathology ; Femoral Fractures - therapy ; Fracture healing ; Fracture Healing - drug effects ; Hematopoietic Stem Cell Mobilization ; Inflammation - pathology ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - drug effects ; Mice ; Osteogenesis - drug effects ; Phenylurea Compounds - pharmacology ; Sex Characteristics</subject><ispartof>Stem cells (Dayton, Ohio), 2016-10, Vol.34 (10), p.2587-2600</ispartof><rights>2016 AlphaMed Press</rights><rights>2016 AlphaMed Press.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5463-afd1345b2960a05ead209bb1277fdc772db5c1515df11d3c4e7f59fa74161fb3</citedby><cites>FETCH-LOGICAL-c5463-afd1345b2960a05ead209bb1277fdc772db5c1515df11d3c4e7f59fa74161fb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27334693$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yao, Wei</creatorcontrib><creatorcontrib>Lay, Yu‐An Evan</creatorcontrib><creatorcontrib>Kot, Alexander</creatorcontrib><creatorcontrib>Liu, Ruiwu</creatorcontrib><creatorcontrib>Zhang, Hongliang</creatorcontrib><creatorcontrib>Chen, Haiyan</creatorcontrib><creatorcontrib>Lam, Kit</creatorcontrib><creatorcontrib>Lane, Nancy E.</creatorcontrib><title>Improved Mobilization of Exogenous Mesenchymal Stem Cells to Bone for Fracture Healing and Sex Difference</title><title>Stem cells (Dayton, Ohio)</title><addtitle>Stem Cells</addtitle><description>Mesenchymal stem cell (MSC) transplantation has been tested in animal and clinical fracture studies. We have developed a bone‐seeking compound, LLP2A‐Alendronate (LLP2A‐Ale) that augments MSC homing to bone. The purpose of this study was to determine whether treatment with LLP2A‐Ale or a combination of LLP2A‐Ale and MSCs would accelerate bone healing in a mouse closed fracture model and if the effects are sex dependent. A right mid‐femur fracture was induced in two‐month‐old osterix‐mCherry (Osx‐mCherry) male and female reporter mice. The mice were subsequently treated with placebo, LLP2A‐Ale (500 μg/kg, IV), MSCs derived from wild‐type female Osx‐mCherry adipose tissue (ADSC, 3 x 105, IV) or ADSC + LLP2A‐Ale.
In phosphate buffered saline‐treated mice, females had higher systemic and surface‐based bone formation than males. However, male mice formed a larger callus and had higher volumetric bone mineral density and bone strength than females. LLP2A‐Ale treatment increased exogenous MSC homing to the fracture gaps, enhanced incorporation of these cells into callus formation, and stimulated endochondral bone formation. Additionally, higher engraftment of exogenous MSCs in fracture gaps seemed to contribute to overall fracture healing and improved bone strength. These effects were sex‐independent.
There was a sex‐difference in the rate of fracture healing. ADSC and LLP2A‐Ale combination treatment was superior to on callus formation, which was independent of sex. Increased mobilization of exogenous MSCs to fracture sites accelerated endochondral bone formation and enhanced bone tissue regeneration. Stem Cells 2016;34:2587–2600</description><subject>Adipose Tissue - cytology</subject><subject>Adipose‐derived stromal cells</subject><subject>Alendronate - pharmacology</subject><subject>Angiogenesis Osteogenesis</subject><subject>Animals</subject><subject>Bone Density - drug effects</subject><subject>Bone‐targeted</subject><subject>Bony Callus - pathology</subject><subject>Dipeptides - pharmacology</subject><subject>Female</subject><subject>Femoral Fractures - pathology</subject><subject>Femoral Fractures - physiopathology</subject><subject>Femoral Fractures - therapy</subject><subject>Fracture healing</subject><subject>Fracture Healing - drug effects</subject><subject>Hematopoietic Stem Cell Mobilization</subject><subject>Inflammation - pathology</subject><subject>Male</subject><subject>Mesenchymal Stem Cell Transplantation</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchymal Stromal Cells - drug effects</subject><subject>Mice</subject><subject>Osteogenesis - drug effects</subject><subject>Phenylurea Compounds - pharmacology</subject><subject>Sex Characteristics</subject><issn>1066-5099</issn><issn>1549-4918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1vEzEQhlcIREvhwB9AlrjAYVt_O74gQUhppUYckrvl3R2nrnbtYO-Whl-P05QKkJA42ZKfeTwzb1W9JviUYEzP8gjDKeWMPamOieC65prMnpY7lrIWWOuj6kXONxgTLmaz59URVYxxqdlx5S-HbYq30KFlbHzvf9jRx4CiQ4u7uIEQp4yWkCG017vB9mhVvkJz6PuMxog-xQDIxYTOk23HKQG6ANv7sEE2dGgFd-izdw5SKYeX1TNn-wyvHs6Tan2-WM8v6quvXy7nH6_qVnDJaus6wrhoqJbYYgG2o1g3DaFKua5VinaNaIkgonOEdKzloJzQzipOJHENO6k-HLTbqRmgayGMyfZmm_xg085E682fL8Ffm028NUJqPMO0CN49CFL8NkEezeBzWya2Aco2DJkxRTUXjP0HSqXCQt5b3_6F3sQphbKIPaWEkoroQr0_UG2KOSdwj30TbPZRm33UZh91Yd_8Pugj-SvbApwdgO--h92_TWa1XizvlT8BtIO0Ww</recordid><startdate>201610</startdate><enddate>201610</enddate><creator>Yao, Wei</creator><creator>Lay, Yu‐An Evan</creator><creator>Kot, Alexander</creator><creator>Liu, Ruiwu</creator><creator>Zhang, Hongliang</creator><creator>Chen, Haiyan</creator><creator>Lam, Kit</creator><creator>Lane, Nancy E.</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201610</creationdate><title>Improved Mobilization of Exogenous Mesenchymal Stem Cells to Bone for Fracture Healing and Sex Difference</title><author>Yao, Wei ; Lay, Yu‐An Evan ; Kot, Alexander ; Liu, Ruiwu ; Zhang, Hongliang ; Chen, Haiyan ; Lam, Kit ; Lane, Nancy E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5463-afd1345b2960a05ead209bb1277fdc772db5c1515df11d3c4e7f59fa74161fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adipose Tissue - cytology</topic><topic>Adipose‐derived stromal cells</topic><topic>Alendronate - pharmacology</topic><topic>Angiogenesis Osteogenesis</topic><topic>Animals</topic><topic>Bone Density - drug effects</topic><topic>Bone‐targeted</topic><topic>Bony Callus - pathology</topic><topic>Dipeptides - pharmacology</topic><topic>Female</topic><topic>Femoral Fractures - pathology</topic><topic>Femoral Fractures - physiopathology</topic><topic>Femoral Fractures - therapy</topic><topic>Fracture healing</topic><topic>Fracture Healing - drug effects</topic><topic>Hematopoietic Stem Cell Mobilization</topic><topic>Inflammation - pathology</topic><topic>Male</topic><topic>Mesenchymal Stem Cell Transplantation</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Mesenchymal Stromal Cells - drug effects</topic><topic>Mice</topic><topic>Osteogenesis - drug effects</topic><topic>Phenylurea Compounds - pharmacology</topic><topic>Sex Characteristics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yao, Wei</creatorcontrib><creatorcontrib>Lay, Yu‐An Evan</creatorcontrib><creatorcontrib>Kot, Alexander</creatorcontrib><creatorcontrib>Liu, Ruiwu</creatorcontrib><creatorcontrib>Zhang, Hongliang</creatorcontrib><creatorcontrib>Chen, Haiyan</creatorcontrib><creatorcontrib>Lam, Kit</creatorcontrib><creatorcontrib>Lane, Nancy E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Stem cells (Dayton, Ohio)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yao, Wei</au><au>Lay, Yu‐An Evan</au><au>Kot, Alexander</au><au>Liu, Ruiwu</au><au>Zhang, Hongliang</au><au>Chen, Haiyan</au><au>Lam, Kit</au><au>Lane, Nancy E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improved Mobilization of Exogenous Mesenchymal Stem Cells to Bone for Fracture Healing and Sex Difference</atitle><jtitle>Stem cells (Dayton, Ohio)</jtitle><addtitle>Stem Cells</addtitle><date>2016-10</date><risdate>2016</risdate><volume>34</volume><issue>10</issue><spage>2587</spage><epage>2600</epage><pages>2587-2600</pages><issn>1066-5099</issn><eissn>1549-4918</eissn><abstract>Mesenchymal stem cell (MSC) transplantation has been tested in animal and clinical fracture studies. We have developed a bone‐seeking compound, LLP2A‐Alendronate (LLP2A‐Ale) that augments MSC homing to bone. The purpose of this study was to determine whether treatment with LLP2A‐Ale or a combination of LLP2A‐Ale and MSCs would accelerate bone healing in a mouse closed fracture model and if the effects are sex dependent. A right mid‐femur fracture was induced in two‐month‐old osterix‐mCherry (Osx‐mCherry) male and female reporter mice. The mice were subsequently treated with placebo, LLP2A‐Ale (500 μg/kg, IV), MSCs derived from wild‐type female Osx‐mCherry adipose tissue (ADSC, 3 x 105, IV) or ADSC + LLP2A‐Ale.
In phosphate buffered saline‐treated mice, females had higher systemic and surface‐based bone formation than males. However, male mice formed a larger callus and had higher volumetric bone mineral density and bone strength than females. LLP2A‐Ale treatment increased exogenous MSC homing to the fracture gaps, enhanced incorporation of these cells into callus formation, and stimulated endochondral bone formation. Additionally, higher engraftment of exogenous MSCs in fracture gaps seemed to contribute to overall fracture healing and improved bone strength. These effects were sex‐independent.
There was a sex‐difference in the rate of fracture healing. ADSC and LLP2A‐Ale combination treatment was superior to on callus formation, which was independent of sex. Increased mobilization of exogenous MSCs to fracture sites accelerated endochondral bone formation and enhanced bone tissue regeneration. Stem Cells 2016;34:2587–2600</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>27334693</pmid><doi>10.1002/stem.2433</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adipose Tissue - cytology Adipose‐derived stromal cells Alendronate - pharmacology Angiogenesis Osteogenesis Animals Bone Density - drug effects Bone‐targeted Bony Callus - pathology Dipeptides - pharmacology Female Femoral Fractures - pathology Femoral Fractures - physiopathology Femoral Fractures - therapy Fracture healing Fracture Healing - drug effects Hematopoietic Stem Cell Mobilization Inflammation - pathology Male Mesenchymal Stem Cell Transplantation Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - drug effects Mice Osteogenesis - drug effects Phenylurea Compounds - pharmacology Sex Characteristics |
| title | Improved Mobilization of Exogenous Mesenchymal Stem Cells to Bone for Fracture Healing and Sex Difference |
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