Hypoxia-Elicited Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Alleviate Myocardial Infarction by Promoting Angiogenesis through the miR-214/Sufu Pathway

<div>miR-214 is involved in MSC<sup>hyp</sup>-sEV-mediated improvement of myocardial repair. (a) Representative echocardiogram of the heart in rats transplanted with PBS, MSC<sup>hyp</sup>-sEVs, MSC<sup>hyp(NC)</sup>-sEVs, and MSC<sup>hyp(inhib)</sup>-sEVs on day 28 post-MI. (b) Rat heart LVEF and LVFE value on various time points of different groups. (c) Representative images of heart sections analyzed with Masson’s staining (<span class="nowrap"><svg height="9.48819pt" id="M36" style="vertical-align:-0.1802893pt" version="1.1" viewbox="-0.0498162 -9.3079 61.9815 9.48819" width="61.9815pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M152 404V712C115 698 54 683 7 677V654C71 648 73 642 73 579V24C128 -2 179 -12 220 -12C353 -12 471 92 471 238C471 357 381 449 274 449C262 449 249 446 233 439L152 404ZM152 374C170 384 202 393 230 393C313 393 382 326 382 213C382 97 330 26 246 26C194 26 165 62 158 81C154 91 152 101 152 116V374Z"></path></g><g transform="matrix(.013,0,0,-0.013,6.669,0)"><path d="M433 39L423 65C413 59 399 54 387 54C370 54 352 69 352 114V299C352 352 342 392 307 422C285 440 255 449 225 449C168 437 102 399 75 379C56 365 44 353 44 339C44 315 69 296 87 296C101 296 111 303 116 319C124 349 133 371 145 385C156 397 171 404 190 404C241 404 275 364 275 291V274C253 256 180 229 120 209C65 190 39 159 39 110C39 47 88 -12 159 -12C189 -12 237 25 277 52C282 35 288 21 301 8C312 -3 333 -12 348 -12L433 39ZM275 84C256 65 221 48 195 48C164 48 124 73 124 124C124 161 146 180 185 198C206 208 254 229 275 240V84Z"></path></g><g transform="matrix(.013,0,0,-0.013,12.259,0)"><path d="M181 342V451C133 431 89 419 40 411V388C98 381 102 377 102 311V104C102 38 95 32 33 26V0H263V26C186 32 181 38 181 104V287C203 343 235 372 261 372C277 372 289 366 304 352C310 346 318 345 330 350C349 359 362 379 362 399C362 422 338 449 304 449C256 449 213 393 183 342H181Z"></path></g><g transform="matrix(.013,0,0,-0.013,20.778,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,32.041,0)"><path d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"></path></g><g transform="matrix(.013,0,0,-0.013,40.456,0)"><path d="M797 0V26C739 32 732 36 732 103V296C732 394 682 449 605 449C576 449 550 437 529 423C504 407 475 389 446 366C425 418 382 449 334 449C303 449 279 437 253 421C222 403 201 385 180 371V452C135 432 85 419 41 411V388C99 379 102 374 102 310V103C102 38 93 32 27 26V0H238V26C189 32 180 38 180 103V338C210 363 250 390 289 390C351 390 377 348 377 275V103C377 37 368 32 306 26V0H520V26C465 32 456 38 456 101V296C456 314 455 326 453 338C491 369 529 390 565 390C628 390 653 345 653 274V107C653 36 642 32 583 26V0H797Z"></path></g><g transform="matrix(.013,0,0,-0.013,51.103,0)"><path d="M797 0V26C739 32 732 36 732 103V296C732 394 682 449 605 449C576 449 550 437 529 423C504 407 475 389 446 366C425 418 382 449 334 449C303 449 279 437 253 421C222 403 201 385 180 371V452C135 432 85 419 41 411V388C99 379 102 374 102 310V103C102 38 93 32 27 26V0H238V26C189 32 180 38 180 103V338C210 363 250 390 289 390C351 390 377 348 377 275V103C377 37 368 32 306 26V0H520V26C465 32 456 38 456 101V296C456 314 455 326 453 338C491 369 529 390 565 390C628 390 653 345 653 274V107C653 36 642 32 583 26V0H797Z"></path></g></svg>).</span> (d) Quantitative data for the left ventricular fibrotic length. (e) CD31 immunofluorescence staining was performed to access angiogenesis at 4 weeks after MI and quantitative data for the capillary density (<span class="nowrap"><svg height="8.32035pt" id="M37" style="vertical-align:-0.2063999pt" version="1.1" viewbox="-0.0498162 -8.11395 27.8368 8.32035" width="27.8368pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M495 86L479 114C446 82 419 66 409 66C401 66 401 72 406 97C420 166 436 231 453 297C489 435 454 448 428 448C406 448 384 439 354 422C305 394 222 327 161 247H159L183 345C200 415 194 448 173 448C143 448 82 410 23 351L38 325C64 349 95 371 105 371C111 371 116 365 109 336L25 -4L31 -12C50 -4 77 3 107 9C119 69 132 122 145 168C197 254 321 381 370 381C387 381 393 374 378 305L329 95C309 17 320 -12 345 -12C372 -12 430 19 495 86Z"></path></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"></path></g><g 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Stem Cells International

fig6

Figure 6

Figure 6: Hypoxia-Elicited Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Alleviate Myocardial Infarction by Promoting Angiogenesis through the miR-214/Sufu Pathway 

Figure 6 | Hypoxia-Elicited Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Alleviate Myocardial Infarction by Promoting Angiogenesis through the miR-214/Sufu Pathway 