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Systematic ReviewUmbilical Cord Tissue Offers the Greatest Number ofHarvestable Mesenchymal Stem Cells for Researchand Clinical Application: A Literature Review ofDifferent Harvest SitesC. Thomas Vangsness Jr., M.D., Hal Sternberg, M.D., and Liam Harris, B.S.Purpose: Recent years have seen dramatic increases in the techniques used to harvest and isolate human mesenchymalstem cells. As the potential therapeutic aspects of these cells further develop, informative data on the differences in yieldsbetween tissue harvest sites and methods will become increasingly valuable. We collected and compared data on cell yieldsfrom multiple tissue harvest sites to provide insight into the varying levels of mesenchymal stem cells by tissue and offerprimary and alternative tissue types for harvest and clinical application. Methods: The PubMed and Medline databaseswere searched for articles relating to the harvest, isolation, and quantification of human mesenchymal stem cells. Selectedarticles were analyzed for relevant data, which were categorized according to tissue site and, if possible, standardized tofacilitate comparison between sites. Results: Human mesenchymal stem cell levels in tissue varied widely according totissue site and harvest method. Yields for adipose tissue ranged from 4,737 cells/mL of tissue to 1,550,000 cells/mL of tissue.Yields for bone marrow ranged from 1 to 30 cells/mL to 317,400 cells/mL. Yields for umbilical cord tissue ranged from10,000 cells/mL to 4,700,000 cells/cm of umbilical cord. Secondary tissue harvest sites such as placental tissue and synoviumyielded results ranging from 1,000 cells/mL to 30,000 cells/mL. Conclusions: Variations in allogeneic mesenchymal stemcell harvest levels from human tissues reflect the evolving nature of the field, patient demographic characteristics, and differences in harvest and isolation techniques. At present, Wharton’s jelly tissue yields the highest concentration of allogeneicmesenchymal stem cells whereas adipose tissue yields the highest levels of autologous mesenchymal stem cells per milliliter oftissue. Clinical Relevance: This comparison of stem cell levels from the literature offers a primer and guide for harvestingmesenchymal stem cells. Larger mesenchymal stem cell yields are more desirable for research and clinical application.See commentary on page 1844Recent advances in stem cell technology havebegun to realize the therapeutic regenerative potential of mesenchymal stem cells (MSCs).1,2 As newexperiments are performed in various fields of medicine,more and more physicians may be able to improve diseaseoutcomes through the use of MSCs. In orthopaedic surgery, MSCs may present a unique opportunity to decreaserecovery time3 and reduce morbidity rates4 amongFrom Keck School of Medicine, University of Southern California (C.T.V.,L.H.), Los Angeles; and Biotime (H.S.), Alameda, California, U.S.A.The authors report that they have no conflicts of interest in the authorshipand publication of this article.Received July 18, 2014; accepted March 12, 2015.Address correspondence to C. Thomas Vangsness Jr., M.D., Keck School ofMedicine, University of Southern California, 1520 San Pablo St., #3800, LosAngeles, CA, U.S.A. E-mail: vangsnes@usc.eduÓ 2015 by the Arthroscopy Association of North America0749-8063/14622/ 41836patients. Disorders such as osteoarthritis,5-7 ligament andtendon repair,8-10 and bone union11 may all benefit fromthe therapeutic application of MSCs in humans. As evidence of the benefits of these procedures grows, moresurgeons will look to provide cellular treatments to theirpatients. At present, there are 502 active human clinicaltrials involving the therapeutic use of MSCs,12 a numberthat is only expected to increase.With these innovations have come new developments for the harvesting and characterization ofMSCs. Advances over the past several years have yielded promising avenues for collecting MSCs for potentialsurgical applications. As the technology for these applications develops, a direct comparison of the qualities,tissue harvest sites, and yields for different sources ofMSCs will become valuable to treating surgeons.To this end, we reviewed the established literatureon MSC sources from different tissue harvest sites forhuman MSCs. The purpose of this study was to provide aArthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 31, No 9 (September), 2015: pp 1836-1843
HARVESTABLE MESENCHYMAL STEM CELLS1837consensus of opinion for the best site and tissue type forMSC harvest through review of established literature.We hypothesized that, despite wide variations inyields between anatomic sites and harvest techniques,placental tissue yields the greatest, most easily accessiblequantity of MSCs for research or clinical application.MethodsSearchFor this study, the PubMed and Medline databaseswere used to conduct a comprehensive search of journal articles related to the qualities, classes, and harvestof human MSCs (Fig 1). The search terms used were asfollows: placental stem cell, adipose stem cell, bonemarrow mesenchymal stem cell, umbilical cordmesenchymal stem cell, amniotic stem cell, chorionicstem cell, mesenchymal stem cell isolation, mesenchymal stem cell harvest, progenitor cell harvest, andmesenchymal stem cell quantification. These searchedterms yielded 25,063 results. Among these results, articles without the keywords “human” and “harvest”were excluded, yielding 1,075 articles. These articleswere evaluated for quality and relevance to this study,after which 161 articles were selected for more detailedanalysis. The bibliographies of these 161 articles werealso searched for relevant publications, ultimatelyyielding 29 articles for review. In addition, theClinicalTrials.gov database was reviewed for relevantclinical trials involving the use of human MSCs.Eligibility Criteria and Data ExtractionThis search was limited to articles published in theEnglish language up to December 31, 2014. Relevantarticles for this survey were studied, and their bibliographies were searched and evaluated for relevant dataconcerning MSC harvest. Articles were analyzed forinformation on different classes of MSCs, cell surfacemarkers, and tissue harvest sites, as well as quantification of cells at these specific harvest sites, with relevantarticles selected for this review based on inclusion ofMSC harvest data. These data were organized bydifferent harvest sites and tissue types to be presentedin a clear and direct format.ResultsThe results of this literature review yielded 4 majortissue sources of MSCs as defined by tissue localization,as well as multiple subclasses. These broad classes wereplacental tissue derived, adipose derived, bone marrowderived, and umbilical cord derived. The synovialmembrane, peripheral blood, umbilical cord blood,periosteum, muscle, and trabecular bone have beenstudied as sources of MSCs, but comparative data aremuch less common. The results of this review aresummarized in Table 1.Fig 1. Comparative histological slides of various Humanmesenchymal stem cell populations from various tissues. (A)Adipose tissue mesenchymal stem cell shown in invertedphase microscopy (magnification unknown; reprinted withpermission56). (B) Bone marrow mesenchymal stem cells.( 10 magnification; reprinted with permission57). (C) Umbilical cord tissue mesenchymal stem cells shown in invertedphase ( 200 magnification; reprinted with permission58). (D)Synovial tissue mesenchymal stem cells shown in alizarin red Sstain ( 200 magnification; reprinted with permission59).AdiposeAdipose tissue harvest by reviewed studies reliedprimarily on a lipoaspiration technique to isolate
1838C. T. VANGSNESS ET AL.Table 1. Reported Mesenchymal Stem Cell Yields From Various Harvest SitesAuthorsRaposio et al.44Minonzio et al.45OedayrajsinghVarma et al.46von Heimburget al.47Policha et al.48Tissue TypeAdiposeAdiposeAdiposeTissue SiteUnknownUnknownAbdomen, hip, thighAdiposeUnknownAdiposeAbdomenGruber et al.49Aust et al.50AdiposeAdiposeAbdomenAbdomenMitchell et al.29AdiposeUnknownYoshimura et al.14AdiposeUnknownZhu et al.36Yu et al.51AdiposeAdiposeUnknownUnknownStrem et al.13De Ugarte et al.16De Ugarte et al.16Wexler et al.33Hernigou et al.32AdiposeAdiposeBone marrowBone marrowBone marrowUnknownUnknownHipUnknownAnterior iliac crestHernigou et al.52Pierini et al.34Bone marrowBone marrowIliac crestPosterior iliac crestPierini et al.34Bone marrowAnterior iliac crestde Girolamo et al.6de Girolamo et al.6Sakaguchi et al.15Sakaguchi et al.21Bone marrowBone marrowBone marrowTrabecular boneIliac crestSubchondral kneeTibiaTibiaSakaguchi et al.21Sakaguchi et al.21Sakaguchi et al.21PeriosteumSynoviumMuscleBongso andFong18Tsagias et al.53Chatzistamatiouet al.54UCTibiaMedial kneeSemitendinosusmuscleWharton’s jellyUCUCWharton’s JellyWharton’s JellyKarahuseyinogluet al.17Weiss et al.35Fu et al.55Lu et al.21UCWharton’s jellyUCUCUCWharton’s jellyWharton’s jellyCord bloodKim et al.18UCWharton’s JellyKim et al.19Zvaifler et al.20Placental tissueBloodChorionPeripheralReported Level5.0 105 cells/80 mL adipose tissue587,753 cells/75.3 g adipose tissue6.3 1.8% of harvested adipose SVF(mean SEM)80,000 to 350,000 cells/g adiposetissue259,345 15,441 cells/g adiposetissue (mean SEM)471,000 cells/mL of adipose tissue404,000 206,000 cells/mLlipoaspirate (mean SD)308,849 nucleated cells/mL oflipoaspirate1.31 0.5 109 and 1.55 0.79 109/L adipose tissue(mean SEM)500,000 cells/1.5 mL of adipose tissue375 142 103/mL of lipoaspirate(mean SD)5,000/g of adipose tissue2 105/g of adipose3 105/g1 in 3.4 104 nucleated cells612 134 cells/mL of bone marrow(mean SD)84 to 7,581 cells/mL269.3 185.1/106 mononuclear cells(mean SD)166 133.8/106 mononuclear cells(mean SD)0.04% of cells0.02% of cells1:105 to 1:106 nucleated cellsApproximately 1:103 to 1:105nucleated cellsApproximately 1:102 nucleated cellsApproximately 1:102 nucleated cellsApproximately 1:102 nucleated cellsConverted Level: Cells perMilliliter of Tissue6,250 cells/mL7,395 cells/mL18,334-61,398 cells/mL75,800-331,625 cells/mL245,729 14,630 cells/mL471,000 cells/mL404,000 cells/mL19,303 cells/mL1,310,000 cells/mL and1,550,000 cells/mL333,333 cells/mL375,000 cells/mL4,737.5 cells/mL189,500 cells/mL317,400 cells/mL612 cells/mL84 to 7,581 cells/mL3,606.94 cells/mL1,942.72 cells/mL1-30 cells/mL1,000-100,000 cells/g30,000 cells/g30,000 cells/g20,000 cells/g4.7 106/cm of UC0.65 106/cm of cord1.75 105 0.94 105 3.02 105 0.66 105 cells/cm(mean SD)10 103/cm of UC1.5 104/cm UC50 103/cm of UCApproximately 1:103 to 1:104nucleated cells6.4 3.2 104 /g wet tissue(mean SEM)4.5 2.7 104/g of wet tissueApproximately 1:103 to 1:104nucleated cells1,000 cells/mL1-40 cells/mLNOTE. Values were reported in mL when reported in mL in the literature, or when accepted densities were available for conversion to mL.Values reported in grams of cm of tissue which could not be converted were reported in their original units.SVF, stromal vascular fraction; UC, umbilical cord.
HARVESTABLE MESENCHYMAL STEM CELLSadipose tissue, and unprocessed lipoaspirate and simpleadipose tissue were evaluated as equivalent substances.Levels for adipose-derived MSCs ranged from 4,737.5MSCs/mL of lipoaspirate13 to 1,550,000 MSCs/mL oflipoaspirate14 (Table 1, Fig 1).Bone MarrowBone marrow tissue harvest was primarily conductedthrough repeated aspirations through large-bore needles, ranging from 15- to 18-gauge sizes.15 Levels forbone marrowederived MSCs ranged from 1 to 30MSCs/mL15 to 317,400 cells/mL16 (Table 1, Fig 1).Umbilical Cord and Placental TissuePlacental tissuee and umbilical cordederived MSCsproved unique in their diverse harvest and tissue-specificharvest sites. Tissue cell levels for Wharton’s jelly (umbilical cord connective tissue) ranged from 10,000 MSCs/mL of umbilical cord17 to 4,700,000 MSCs/cm of umbilical cord.18 Chorionic tissue cell levels were reported to be45,000 MSCs/g of wet tissue (Fig 1).19Peripheral TissuePeripheral blood, which was collected through peripheral blood draw and centrifugation, was reported tohave MSC levels of 1 to 40 cells/mL.20 Muscle tissuewas harvested from the semitendinosus tendon, whichwas collected with a tendon stripper.21 Similarly, periosteum tissue was collected from the tibial insertion ofthe same harvested semitendinosus tendon.21 Synovialtissue was harvested during arthroscopic surgery fromthe medial joint capsule of the knee using a pituitaryrongeur.21DiscussionThe advancement of stem cell transplant techniquesover recent years has made the practical acquisition ofthese cells increasingly worthwhile for the purpose ofreconstructive surgery. Autologous sources representthe most current, cost-efficient, and least controversialoption to acquire and transplant MSCs in the clinicalsetting. Physicians and researchers exploring thisemerging field will require resources conciselyexplaining the most efficient sites for MSC harvest, aswell as the levels of cells available in different tissues.Determining the best and most consistent tissue sourceof human MSCs, as well as the cell levels typicallyharvested from related sites, offers a valuable resourcefor future clinical studies.Given the diverse array of units used to report cellharvest levels among selected studies, values wereconverted to a standard measurement to allow directcomparison between studies and tissues. For adiposevalues, a common value for the density of adiposetissue was selected from previous studies as 0.9475g/mL22 to convert values from grams to milliliters. The1839standard density for bone marrow used for conversionswas determined to be 1.058 g/mL.23 Values fromstudies that did not include volume or mass data forbone marrow harvest could not be reported in milliliters and, consequently, were reported with MSCs as apercentage of total nucleated cells. Similar concernsarose in the reporting of umbilical cord tissue. Valuesfrom studies that did not include mass or volume datawere instead recorded by length of cord and could notbe converted.Autograft Tissue and Minimal ManipulationComparisons of yields between placental and autografttissue invite clarification of the practical difference between autograph and allograph transplantation, as wellas minimally manipulated tissues. Allograft tissue rarelypresents with immune complications after transplantation. The lack of the human leukocyte antigeneAsurface antigen confers an immune-privileged nature toplacental tissue, allowing for comparable use of the 2tissues without immune-modifying therapy.24 Consequently, for the purposes of clinical use and this review,allograft placental tissue is comparable with autograftcells.According to US Food and Drug Administration (FDA)regulations, only cellular products classified as “361 tissue” may be exempt from premarket review and regulation. Classification as 361 tissue requires cells to be“minimally manipulated,” a criterion that excludesmany common techniques used to harvest, isolate, andpurify MSCs today. It should be noted that adipose tissuecurrently harvested for MSCs requires multistep processing, including enzymatic digestion, purification, andexpansion in culture, which is considered more than“minimal manipulation,” thereby excluding them from361 cellular tissue classification by the FDA.25 However,recent procedural and technologic advances havedemonstrated efficient, non-enzymatic purification ofhuman MSCs from lipoaspirate.26 Further, recentstudies have shown mechanically purified adiposederived MSCs demonstrate greater pluripotent responsecompared to enzymatically isolated adipose stem cells.27Given recent FDA approval for marketing of this systemand subsequent “361 cellular tissue” classification, thefield of adipose-derived stem cells and their clinicalapplication may greatly expand in the coming years. Inaddition, a 2013 update by the FDA Tissue ReferenceGroup clarified that bone marrow MSCs, whenexpanded in culture, did not fall under the classificationof 361 cells.28 Consequently, the advancement of thefield and therapeutic application of MSCs will likely relyon the ability to harvest cells in quantities suitable forimplantation without digestion and expansion. Adetailed understanding of the anatomic sites and tissuetypes yielding the highest levels and concentrations ofcells by volume will prove crucial to these initial steps.
1840C. T. VANGSNESS ET AL.Technologic developments to further purify MSCs fromharvest tissue without the use of expansion in culturewill allow researchers to rapidly expand both the academic and clinical applications of these cells. Indeed,novel “non-manipulating” measures to efficientlyextract MSCs from adipose tissue are currently beingexplored,29 which will likely allow for the circumvention of 361 regulations for clinical study and application.Our results indicate significant differences in thequantity and consistency of stem cell levels betweenadipose, bone marrow, and placental tissues. Studiesperforming harvest and isolation of MSCs from adiposetissue consistently showed higher cell yields thanwith MSCs from bone marrow and placental tissue.Furthermore, variations in harvest levels betweendifferent studies of the same tissue indicate notabledifferences. The highest reported yield for studies onadipose tissue showed an over 300-fold increase in cellharvest over the lowest reported values.13,14 Bonemarrow studies showed an over 1,000-fold increasebetween the highest and lowest reported yields.15,16This large variation must be noted.Quantification of CellsPertinent to the analysis of cell yields from varioustissues is the methods by which yields were quantified.Cellular quantification techniques proved relativelyhomogeneous across both tissue subtype and anatomicsite. The primary method of cell harvest quantificationwas a limited-dilution colony-forming unit assay. Tissues were harvested and homogenized by serialcentrifugation and suspension in liquid media according to techniques and concentrations specific to eachanatomic site. Purification of MSCs was performed byserial replacement of cellular growth media and subsequent disposal of nonadherent cells using the innatecellular adhesion properties of MSCs.30 Rough celldensities in liquid media were determined using cellcounters and hemocytometers, after which cells wereplated at densities ranging from 103 cells per plate20 to106 cells per plate.31 After growth of fibroblast colonies,cells were stained and counted using light microscopy.Studies conducted by Mitchell et al.,31 Wexler et al.,32Hernigou et al.,33 Pierini et al.,34 Sakaguchi et al.,21Weiss et al.,35 and Lu et al.22 all used the limiteddilution fibroblast colony-forming unit assay. Amongthese studies, notable variables included the timeallowed for colony growth, which varied from 7 to 14days; the number of cells determined to define a “colony,” which ranged from 20 cells per colony31 to 50cells per colony33; and the number of serial dilutionsconducted beforehand to purify the cells. Because theanatomic tissue source of each cell type necessitatesdifferent methods of initial preparation, comparison ofhomogenization and serial dilution is impractical, andthis variable should be noted. Alternative quantificationmethods used serial dilution and cellular adherence,followed immediately by cell quantification using cellcounters. This technique was used by Zhu et al.,36 DeUgarte et al.,16 Yoshimura et al.,14 and Zvaifler et al.20Finally, de Girolamo et al.6 used flow cytometry toquantify cellular harvest levels, incubating cells withcommercial anti-CD45 and anti-CD271 antibodies afterserial dilution and purification using cellular adherence.Differences in quantification are likely to yield significant variations in harvest levels. As shown by Cuthbertet al.,37 Jones et al.,38 and Tormin et al.,39 roughly 1 in17 CD271-positive cells yield a fibroblast colony duringcolony-forming unit assay. Although these potentialdifferences did not influence our conclusions, in thefuture, consideration must be given to the method ofcellular quantification.Variations in YieldsDifferences in yields among tissue sites are likely aresult of 2 principal factors: harvest techniques andpatient demographic characteristics. Adipose tissueederived MSC yields have been shown to be onlyminimally affected by age differences among patients.40Given the multistep process of harvesting and isolatingadipose tissueederived MSCs, differences in yields maybe principally a consequence of variations in harvesttechniques. Procedural variations in enzymatic digestion, buffer selection, and centrifugation can all havesignificant impacts on MSC yields.41 Despite this,analysis of our results indicates that in addition tohigher levels of cells, adipose tissue maintains decidedlygreater consistency in stem cell density as comparedwith alternative primary harvest sites. We believe thisconsistency results from both the more homogeneousnature of the tissue as compared with bone marrowand, paradoxically, the more procedurally involvedmanner of its harvest. The complex nature of MSCharvest from adipose tissue necessitates following oradapting proven procedures. Consequently, large mechanical differences in harvesting which lead to variations in yield, such as marrow aspiration technique,were largely eliminated. Concurrently, smaller differences were increased through the introduction of variations in enzyme and buffer concentrations.Bone marrowederived MSC yields showed significant variation likely because of differences in both theanatomic harvest site and patient demographic characteristics. Studies by Pierini et al.34 and de Girolamoet al.6 showed up to a 2-fold differences in yields between various marrow sites in the body. In particular,Pierini et al. concluded that the posterior iliac crest wasthe optimal harvest site for MSCs, above both theanterior iliac crest and the subchondral knee. Furthermore, evidence has shown that the use of the iliac crestas a harvest site, a common site in our review, predisposes harvest samples to significant dilution by
HARVESTABLE MESENCHYMAL STEM CELLSperipheral blood,37 resulting in both depressed valuesand increased variation in harvest yields. In addition,increased age, particularly among women, has beenshown to have a significant impact on bonemarrowederived MSC harvest yields, with numerousstudies having shown bone marrowederived MSCyields to decrease with age.42,43 Because selectedstudies used a diverse range of donor ages, decreasedyields compared with other studies are likely affected byincreasing donor age and should be considered byphysicians planning future MSC harvests. Finally, thesedata on harvest numbers of MSCs by anatomic site andtissue type offer no predictive information about thecellular activity of the individual MSCs. Differences instem cell biology between and among these tissuesources must be evaluated in the laboratory and clinicas we proceed with this new field of biology.LimitationsLimitations to our study primarily concerned issues oftissue comparability and scope of the initial search. Asmentioned previously, conversion to common units(milliliters) for direct comparison of tissues wasdependent on the existence of accepted values for tissuedensity. Consequently, umbilical cord stromal tissues,as well as certain reported bone marrow values, couldnot be converted to common units for directcomparison.Initial development of the search criteria excludedarticles that had not been translated into English. Inaddition, articles that were not accessible through thePubMed or Medline databases were excluded from ourinitial search. Although bibliographies of initiallyselected articles were evaluated for relevant publications and data, this limitation must be acknowledged.ConclusionsLarge variations in cell harvest yields remain for eachmajor tissue site for MSCs as reported in the literatureto date. Reviewed research supports the understandingthat placental tissue provides the highest concentrationof cells whereas adipose tissue offers the highest levelsof autologous cells. Consequently, considerations mustbe made regarding the non-autologous nature of umbilical cordederived stem cells, as well as the increasedpost-harvest processing required for adipose-derivedstem cells, for the purposes of research and clinicalapplication.References1. Pak J, Lee JH, Lee SH. A novel biological approach to treatchondromalacia patellae. PLoS One 2013;8:e64569.2. Vangsness CT, Farr J, Boyd J, Dellaero DT, Mills CR,LeRoux-Williams M. Adult human mesenchymal stemcells delivered via intra-articular injection to the kneefollowing partial medial meniscectomy: A 8.1841double-blind, controlled study. J Bone Joint Surg Am2014;96:90-98.Kitoh H, Kitakoji T, Tsuchiya H, Katoh M, Ishiguro N.Transplantation of culture expanded bone marrow cellsand platelet rich plasma in distraction osteogenesis of thelong bones. Bone 2007;40:522-528.Ellera Gomes JL, da Silva RC, Silla LM, Abreu MR,Pellanda R. Conventional rotator cuff repair complementedby the aid of mononuclear autologous stem cells. Knee SurgSports Traumatol Arthrosc 2012;20:373-377.Aicher WK, Bühring HJ, Hart M, Rolauffs B, Badke A,Klein G. Regeneration of cartilage and bone by definedsubsets of mesenchymal stromal cellsdPotential and pitfalls. Adv Drug Deliv Rev 2011;63:342-351.de Girolamo L, Bertolini G, Cervellin M, Sozzi G, Volpi P.Treatment of chondral defects of the knee with one stepmatrix-assisted technique enhanced by autologousconcentrated bone marrow: In vitro characterisation ofmesenchymal stem cells from iliac crest and subchondralbone. Injury 2010;41:1172-1177.Orozco L, Munar A, Soler R, et al. Treatment of kneeosteoarthritis with autologous mesenchymal stem cells: Apilot study. Transplantation 2013;95:1535-1541.Ahmad Z, Wardale J, Brooks R, Henson F, Noorani A,Rushton N. Exploring the application of stem cells in tendonrepair and regeneration. Arthroscopy 2012;28:1018-1029.Clarke AW, Alyas F, Morris T, Robertson CJ, Bell J,Connell DA. Skin-derived tenocyte-like cells for thetreatment of patellar tendinopathy. Am J Sports Med2011;39:614-623.Connell D, Datir A, Alyas F, Curtis M. Treatment of lateralepicondylitis using skin-derived tenocyte-like cells. Br JSports Med 2009;43:293-298.Liebergall M, Schroeder J, Mosheiff R, et al. Stem cellbased therapy for prevention of delayed fracture union:A randomized and prospective preliminary study. MolTher 2013;21:1631-1638.National Institutes of Health ClinicalTrials.gov Database.Available at ClinicalTrials.gov. Accessed May 13, 2015.Strem BM, Hicok KC, Zhu M, et al. Multipotentialdifferentiation of adipose tissue-derived stem cells. Keio JMed 2005;54:132-141.Yoshimura K, Shigeura T, Matsumoto D, et al. Characterization of freshly isolated and cultured cells derivedfrom the fatty and fluid portions of liposuction aspirates.J Cell Physiol 2006;208:64-76.Sakaguchi Y, Sekiya I, Yagishita K, Ichinose S,Shinomiya K, Muneta T. Suspended cells from trabecularbone by collagenase digestion become virtually identicalto mesenchymal stem cells obtained from marrow aspirates. Blood 2004;104:2728-2735.De Ugarte DA, Morizono K, Elbarbary A, et al. Comparison of multi-lineage cells from human adipose tissue andbone marrow. Cells Tissues Organs 2003;174:101-109.Karahuseyinoglu S, Cinar O, Kilic E, et al. Biology of stemcells in human umbilical cord stroma: in situ and in vitrosurveys. Stem Cells 2007;25:319-331.Bongso A, Fong CY. The therapeutic potential, challengesand future clinical directions of stem cells from theWharton’s jelly of the human umbilical cord. Stem Cell Rev2013;9:226-240.
1842C. T. VANGSNESS ET AL.19. Kim MJ, Shin KS, Jeon JH, et al. Human chorionic-platederived mesenchymal stem cells and Wharton’s jellyderived mesenchymal stem cells: A comparative analysisof their potential as placenta-derived stem cells. Cell TissueRes 2011;346:53-64.20. Zvaifler NJ, Marinova-Mutafchieva L, Adams G, et al.Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res 2000;2:477-488.21. Sakaguchi Y, Sekiya I, Yagishita K, Muneta T. Comparisonof human stem cells derived from various mesenchymaltissues: Superiority of synovium as a cell source. ArthritisRheum 2005;52:2521-2529.22. Lu LL, Liu YJ, Yang SG, et al. Isolation and characterizationof human umbilical cord mesenchymal stem cells withhematopoiesis-supportive function and other potentials.Haematologica 2006;91:1017-1026.23. Gee AP. Bone marrow purging and processingeA reviewof ancillary effects. Prog Clin Biol Res 1990;333:507-521.24. Stubbendorff M, Deuse T, Hua X, et al. Immunologicalproperties of extraembryonic human mesenchymal stromal cells derived from gestational tissue. Stem Cells Dev2013;22:2619-2629.25. US Food and Drug Administration. Guidance for industryand FDA staff: Minimal manipulation of structural tissue(jurisdictional update). Silver Spring, MD: US Food andDrug Administration; 2006.26. Bianchi F, Maioli M, Leonardi E, et al. A new nonenzymatic method and device to obtain a fat tissue derivativehighly enriched in pericyte-like elements by mild mechanical forces from human lipoaspirates. Cell Transplant2013;22:2063-2077.27. Maioli M, Rinaldi S, Santaniello S, et al. Radioelectricasymmetric conveyed fields and human adipose-derivedstem cells obtained with a nonenzymatic method anddevice: A novel approach to multipotency. Cell Transplant2014;23:1489-1500.28. US Food and Drug Administration. Tissue ReferencesGroup. FY 2013 update. An update on criteria for classification of “361 tissue.” Silver Spring, MD: US Food andDrug Administration; 2013.29. Wu AY, Morrow DM. Clinical use of dieletrophoresisseparation for live adipose derived stem cells. J Transl Med2012;10:99.30. Dominici M, Le Blanc K, Mueller I, et al. Minimal criteriafor defining multipotent mesenchymal stromal cells. TheI
mesenchymal stem cells. Larger mesenchymal stem cell yields are more desirable for research and clinical application. See commentary on page 1844 R ecent advances in stem cell technology have begun to realize the therapeutic regenerative po-tential of mesenchymal stem cells (MSCs).1,2 As new experiments are performed in various fields of medicine,
May 02, 2018 · D. Program Evaluation ͟The organization has provided a description of the framework for how each program will be evaluated. The framework should include all the elements below: ͟The evaluation methods are cost-effective for the organization ͟Quantitative and qualitative data is being collected (at Basics tier, data collection must have begun)
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The Umbilical Cord Embryology By end of 3rd week of development embryo attached to placenta by a connecting stalk comprosed of 5 structures By the end of 1st trimester structures disappear Omphalo-enteric duct (Meckel's diverticulum) Umbilical vesicle of the allantois (Umbilical ligament) Vitelline circulation system in the extra-embryonic region
Chính Văn.- Còn đức Thế tôn thì tuệ giác cực kỳ trong sạch 8: hiện hành bất nhị 9, đạt đến vô tướng 10, đứng vào chỗ đứng của các đức Thế tôn 11, thể hiện tính bình đẳng của các Ngài, đến chỗ không còn chướng ngại 12, giáo pháp không thể khuynh đảo, tâm thức không bị cản trở, cái được
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