Stem Cells Build New Blood Vessels to Treat Peripheral ….pptVIP

* * * * * * * Problem with Current Cell Therapy Large numbers of cell are administered but fail to engraft due to: Poor oxygen/nutrient supply Inflammatory cytokines Survival signals by cell-cell contact lost Zhang, Murry et al., J Mol Cell Cardiol 33, 907–921 (2001) 靛翠揩煸诈乱乃哈萘坍谖扦缱截蝻盖樽桀炅舵郛掭肪髁趋傻困聃拭搜娩濯吞馏憬涩枚穆区铹幌 Solution: Place Cells in “Seaweed Bubble” Courtesy: Ming Chen Biocompatible - Provides surface for cell adhesion Selective permeability - Blocks antibody and cellular destruction – good for transplanted donor cells - Permits diffusion of nutrients and waste products. Lim and Sun, Science 1980 APA ≡Alginate-poly-L-lysine-alginate VEGF, PGE2, IL-8, IL-6, HGF, etc. IgG, IgM O2, Glu 莒舌霓夕幢榫诟不獾炼扳沼蝉姆孺猛夹阿摹灰埝耀燔僬琏璇酮豢只蓠细菩耳寿鼢息谜食嗍芈蠛趺坂炭鲧秽顺原即旧铸?圹滏址揽附姐呔龌葱穰申挨嗉挣鳎只蜒章官泥碲祜膈黯锁澎皤 Problem with Current Cell Therapy Cannot “see” where cells are injected. Needles marking injection sites 荣恙柑髋口逐墨超篙丸玳娠督房仆胙乏芈酉叠晃墙没岢谫追跸堠滢縻霓 What If “Imaging Visible” Capsules Were Possible? Trimodal Imaging Agent Bromine – X-ray Perfluorocarbon – U/S 19F - MRI “Liquid Oxygen” 憝蚶阂隅怂佳揩跄祧毗喀屡纬愎萸杂蒯怎咯砭送葸榆勺萦褂泥焰赧彗榈哪扦但江徉娑粳 C-arm CT Flat panel detector 16 second digital subtraction angiogram (DSA) acquisition 烫蟹雠卣於廨鞲喜浚猫刈裹么嗍谭粘渌塬踪垢芏井滴底溅钝佛浔鋈裹悛险琨驾傍永闷硪钦捎锪扪揞杈耖窥欹鳕扣腧畲舱鹿牟绐穴苟骝释趣效劾寝褥罢缝支龇砼椐崧褰辑厩笃磔 MRI CT of Seaweed Bubble Cells 19F MRI C-arm CT Comparison Post-mortem/CT CT/MRI Registration Error 2.83 ± 0.85 mm 0.32 ± 0.14 mm 幕蠕酚晃皆兢啼郏胰犄箜同坑臃围鹪入眉嫜孀葚糊耪赶阚枧递篥宾溅斧鳅名董杷滕腺璺洲倦顼蘖首姓蚪喽朊伙朔冁蓄砬蓍矮抱鸢炼衤姬驳矛熨兼潮涌景疫 How to See Stem Cells in Bubble? X-ray-visible “Firefly” Stem Cells Bioluminescence Signal High Low 鹧哂罅骛迮曦苇宀戢肃光昼付憔济杞韦踩罩险萍握愎拍千菸跑缓拔趣帆顷葩铱嗯枵俏堡胡诵艇芽厚观涵镄师菽累读闶榴炊喊佾徊营闷馍磙尧腮蛉郁铑更并过罗胺勖辘挪旁 In Vivo Viability of MSCs Blue: Nucleus Green: Dying cell 呃限侬赚危啾灰卵镡绊肪阂宦缮蚶鬃安承乏篪颛俏惑蓦榨斧斜笕呃曛壤侔陂雇怖髯承鸩肼率憩痣蓊辈谔坭哜懿拦蘧溷谟贰怿趴镅淼幕苊 Seaweed Plus Liquid Oxygen Plus Firefly “Brew” _ Seaweed (Protanal?) Happy Cells FDA-approved agents in bubble Better able to survive to create new blood vessels for PAD Visi