%PDF-1.6
%
1 0 obj
<>
endobj
2 0 obj
<>stream
Tomas de Mayo, Paulette Conget, Silvia Becerra-Bayona, Claudia L. Sossa, Virgilio Galvis, Martha L. Arango-Rodríguez
The role of bone marrow mesenchymal stromal cell derivatives in skin wound healing in diabetic mice
www.plosone.org
www.plosone.org
endstream
endobj
3 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 13 0 R/Contents 14 0 R/TrimBox[0 0 612 792]>>
endobj
13 0 obj
[15 0 R 16 0 R 17 0 R 18 0 R 19 0 R 20 0 R 21 0 R 22 0 R 23 0 R 24 0 R 25 0 R 26 0 R 27 0 R 28 0 R 29 0 R 30 0 R 31 0 R 32 0 R 33 0 R 34 0 R 35 0 R 36 0 R 37 0 R 38 0 R 39 0 R 40 0 R 41 0 R 42 0 R 43 0 R]
endobj
15 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref001)>>
endobj
16 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref002)>>
endobj
17 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref003)>>
endobj
18 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref004)>>
endobj
19 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref005)>>
endobj
20 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref006)>>
endobj
21 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref007)>>
endobj
22 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref008)>>
endobj
23 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref009)>>
endobj
24 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref010)>>
endobj
25 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref011)>>
endobj
26 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref012)>>
endobj
27 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref013)>>
endobj
28 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref014)>>
endobj
29 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref015)>>
endobj
30 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref016)>>
endobj
31 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref017)>>
endobj
32 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref018)>>
endobj
33 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref019)>>
endobj
34 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref020)>>
endobj
35 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref021)>>
endobj
36 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref022)>>
endobj
37 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref026)>>
endobj
38 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref027)>>
endobj
39 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref028)>>
endobj
40 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref029)>>
endobj
41 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref030)>>
endobj
42 0 obj
<>/Border[0 0 0]/Dest(Rpone.0177533.ref031)>>
endobj
43 0 obj
<>/Border[0 0 0]/A 44 0 R>>
endobj
44 0 obj
<>
endobj
14 0 obj
[45 0 R 46 0 R 47 0 R 48 0 R 49 0 R 50 0 R 51 0 R 52 0 R 53 0 R 54 0 R 55 0 R 56 0 R 57 0 R 58 0 R 59 0 R 60 0 R 61 0 R 62 0 R 63 0 R 64 0 R 65 0 R 66 0 R 67 0 R 68 0 R 69 0 R 70 0 R 71 0 R 72 0 R 73 0 R 74 0 R]
endobj
45 0 obj
<>stream
q
0.45 0.36 0.35 0.01 k
0 w
575.9997 652.2299 m
199.9998 652.2299 l
199.9998 652.7299 l
575.9997 652.7299 l
f*
0.83 0.64 0.02 0 k
251.6031 549.9213 m
256.3654 549.9213 l
h
f*
402.2362 523.8992 m
406.9984 523.8992 l
h
f*
305.4614 484.8945 m
310.2236 484.8945 l
h
f*
538.6394 445.9465 m
543.4016 445.9465 l
h
f*
547.8803 445.9465 m
552.5858 445.9465 l
h
f*
292.7622 432.9071 m
297.5244 432.9071 l
h
f*
422.3055 432.9071 m
427.0677 432.9071 l
h
f*
534.3874 432.9071 m
539.0929 432.9071 l
h
f*
357.6756 419.9244 m
362.3811 419.9244 l
h
f*
521.7449 419.9244 m
531.2693 419.9244 l
h
f*
346.8472 406.9417 m
356.3717 406.9417 l
h
f*
554.6268 393.9024 m
564.1512 393.9024 l
h
f*
203.4142 354.8976 m
212.9386 354.8976 l
h
f*
301.7764 354.8976 m
311.3008 354.8976 l
h
f*
384.0378 354.8976 m
393.5622 354.8976 l
h
f*
458.9858 354.8976 m
468.5102 354.8976 l
h
f*
472.989 354.8976 m
482.4567 354.8976 l
h
f*
560.6362 354.8976 m
570.1606 354.8976 l
h
f*
200.0126 341.915 m
209.537 341.915 l
h
f*
278.8157 341.915 m
288.3402 341.915 l
h
f*
380.9764 341.915 m
390.5008 341.915 l
h
f*
256.0252 289.9276 m
265.5496 289.9276 l
h
f*
270.7654 289.9276 m
280.2331 289.9276 l
h
f*
331.2567 237.9402 m
340.7811 237.9402 l
h
f*
345.2031 237.9402 m
354.7276 237.9402 l
h
f*
497.2535 185.8961 m
506.7213 185.8961 l
h
f*
393.1087 159.9307 m
402.6331 159.9307 l
h
f*
224.9575 107.9433 m
234.4252 107.9433 l
h
f*
0 g
1 j
1 J
9.5 0 0 9.5 200.0125 707.7543 cm
BT
/F0 1 Tf
1 TL
-0.0042 Tc
0 0 Td
(acd-mMSCs,)Tj
5.9557 0 Td
(the)Tj
1.5933 0 Td
(administratio)Tj
5.6037 0 Td
(n)Tj
0.7698 0 Td
(of)Tj
1.0443 0 Td
(allo-mBM-MSCs)Tj
7.4357 0 Td
(is)Tj
0.931 0 Td
(insufficient)Tj
4.8875 0 Td
(for)Tj
1.3726 0 Td
(wound)Tj
3.133 0 Td
(healing)Tj
3.3896 0 Td
(in)Tj
0.9847 0 Td
(dia-)Tj
-37.1009 -1.474 Td
(betic)Tj
2.3035 0 Td
(mice)Tj
2.3094 0 Td
(and)Tj
1.8679 0 Td
(delays)Tj
3.0734 0 Td
(the)Tj
1.5993 0 Td
(therapeutic)Tj
5.1083 0 Td
(effect,)Tj
2.9242 0 Td
(which)Tj
2.7391 0 Td
(maybe)Tj
3.1927 0 Td
(explained)Tj
4.4399 0 Td
(by)Tj
1.2652 0 Td
(the)Tj
1.5993 0 Td
(fact)Tj
1.8202 0 Td
(that)Tj
1.8678 0 Td
(trophic)Tj
-36.1102 -1.474 Td
(factors)Tj
3.1867 0 Td
(secreted)Tj
4.0102 0 Td
(by)Tj
1.2532 0 Td
(MSCs)Tj
2.9182 0 Td
(are)Tj
1.6411 0 Td
(critical)Tj
3.0077 0 Td
(for)Tj
1.3666 0 Td
(skin)Tj
1.9694 0 Td
(regeneration,)Tj
6.0333 0 Td
(and)Tj
1.8559 0 Td
(not)Tj
1.5874 0 Td
(the)Tj
1.5874 0 Td
(cells)Tj
2.1842 0 Td
(per)Tj
1.6411 0 Td
(se,)Tj
1.5336 0 Td
(suggest-)Tj
-35.776 -1.474 Td
(ing)Tj
1.5336 0 Td
(that)Tj
1.8679 0 Td
(MSCs)Tj
2.9301 0 Td
(may)Tj
2.0947 0 Td
(require)Tj
3.2882 0 Td
(some)Tj
2.6436 0 Td
(time)Tj
2.0947 0 Td
(to)Tj
1.0443 0 Td
(secrete)Tj
3.4672 0 Td
(these)Tj
2.6377 0 Td
(factors)Tj
3.1987 0 Td
(after)Tj
2.2021 0 Td
(their)Tj
2.1364 0 Td
(administration.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 593.9716 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Introduction)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 577.0204 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Ideal)Tj
2.1883 0 Td
(healing)Tj
3.1351 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.6519 0 Td
(skin)Tj
1.8936 0 Td
(wound)Tj
3.016 0 Td
(requires)Tj
3.4696 0 Td
(an)Tj
1.2076 0 Td
(integration)Tj
4.6487 0 Td
(of)Tj
1.0148 0 Td
(complex)Tj
3.6227 0 Td
(biological)Tj
4.0875 0 Td
(and)Tj
1.7292 0 Td
(molecular)Tj
-31.6798 -1.3039 Td
(events)Tj
2.7269 0 Td
(of)Tj
1.0148 0 Td
(cell)Tj
1.559 0 Td
(migration)Tj
4.2009 0 Td
(and)Tj
1.7291 0 Td
(proliferation,)Tj
5.4936 0 Td
(extracellular)Tj
5.1306 0 Td
(matrix)Tj
2.8743 0 Td
(deposition,)Tj
4.6715 0 Td
(angiogenesis,)Tj
5.5162 0 Td
(and)Tj
-34.9169 -1.2982 Td
(remodeling)Tj
4.8188 0 Td
([)Tj
0.83 0.64 0.02 0 k
(1)Tj
0 g
(].)Tj
1.5987 0 Td
(Impairment)Tj
5.0627 0 Td
(of)Tj
1.0148 0 Td
(any)Tj
1.6554 0 Td
(of)Tj
1.0148 0 Td
(such)Tj
2.0636 0 Td
(processes)Tj
3.9685 0 Td
(would)Tj
2.7099 0 Td
(lead)Tj
1.8538 0 Td
(to)Tj
1.0262 0 Td
(wound)Tj
3.0104 0 Td
(chronicity.)Tj
4.5354 0 Td
(Despite)Tj
-34.333 -1.2983 Td
(having)Tj
2.9139 0 Td
(numerous)Tj
4.3087 0 Td
(causes,)Tj
2.9763 0 Td
(wound)Tj
3.0161 0 Td
(chronicity)Tj
4.3086 0 Td
(is)Tj
0.8447 0 Td
(primarily)Tj
3.9685 0 Td
(associated)Tj
4.2576 0 Td
(with)Tj
2.0013 0 Td
(diabetes,)Tj
3.685 0 Td
(atherosclero-)Tj
-32.2807 -1.3039 Td
(sis,)Tj
1.4343 0 Td
(venous/pressure)Tj
6.7294 0 Td
(ulcers,)Tj
2.7949 0 Td
(vasculitis,)Tj
4.0876 0 Td
(and)Tj
1.7291 0 Td
(trauma)Tj
3.1067 0 Td
([)Tj
0.83 0.64 0.02 0 k
(2)Tj
0 g
(].)Tj
1.5988 0 Td
(Given)Tj
2.6305 0 Td
(the)Tj
1.4683 0 Td
(increasing)Tj
4.3313 0 Td
(prevalence)Tj
4.4844 0 Td
(of)Tj
-34.3953 -1.2983 Td
(chronic)Tj
3.2881 0 Td
(wounds)Tj
3.3732 0 Td
(worldwide,)Tj
4.6885 0 Td
(and)Tj
1.7291 0 Td
(their)Tj
2.109 0 Td
(marked)Tj
3.2882 0 Td
(outcomes)Tj
4.0875 0 Td
(on)Tj
1.2756 0 Td
(patient)Tj
3.0103 0 Td
(morbidity)Tj
4.2406 0 Td
(and)Tj
1.7292 0 Td
(mortality)Tj
-32.8193 -1.2982 Td
(\(let)Tj
1.525 0 Td
(alone)Tj
2.3811 0 Td
(amputations\),)Tj
5.7996 0 Td
(it)Tj
0.7824 0 Td
(is)Tj
0.8504 0 Td
(crucial)Tj
2.914 0 Td
(to)Tj
1.0261 0 Td
(consider)Tj
3.6453 0 Td
(adequate)Tj
3.7984 0 Td
(and)Tj
1.7291 0 Td
(effective)Tj
3.5093 0 Td
(interventions)Tj
5.5389 0 Td
(to)Tj
1.0261 0 Td
(treat)Tj
-34.5257 -1.304 Td
(such)Tj
2.0579 0 Td
(debilitating)Tj
4.7735 0 Td
(wounds)Tj
3.3732 0 Td
([)Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
(].)Tj
-9.0084 -1.2982 Td
(Multipotent)Tj
5.0456 0 Td
(mesenchymal)Tj
5.7033 0 Td
(stromal)Tj
3.2598 0 Td
(cells,)Tj
2.143 0 Td
(also)Tj
1.7688 0 Td
(referred)Tj
3.4185 0 Td
(to)Tj
1.0262 0 Td
(as)Tj
1.0148 0 Td
(mesenchymal)Tj
5.7032 0 Td
(stem)Tj
2.1203 0 Td
(cells)Tj
-32.3997 -1.2983 Td
(\(MSCs\),)Tj
3.5149 0 Td
(are)Tj
1.4513 0 Td
(an)Tj
1.2019 0 Td
(outstanding)Tj
5.006 0 Td
(tool)Tj
1.7744 0 Td
(for)Tj
1.389 0 Td
(cell)Tj
1.559 0 Td
(therapy)Tj
3.2485 0 Td
(applications,)Tj
5.2668 0 Td
(not)Tj
1.5703 0 Td
(only)Tj
1.9786 0 Td
(because)Tj
3.3165 0 Td
(of)Tj
1.0148 0 Td
(their)Tj
2.109 0 Td
(multi-)Tj
-34.401 -1.2983 Td
(potent)Tj
2.8119 0 Td
(nature,)Tj
3.0501 0 Td
(but)Tj
1.5533 0 Td
(also)Tj
1.7688 0 Td
(due)Tj
1.6952 0 Td
(to)Tj
1.0261 0 Td
(their)Tj
2.1089 0 Td
(ability)Tj
2.6929 0 Td
(to)Tj
1.0262 0 Td
(home)Tj
2.5001 0 Td
(and)Tj
1.7291 0 Td
(engraft)Tj
3.0501 0 Td
(into)Tj
1.8368 0 Td
(damaged)Tj
3.8551 0 Td
(tissues)Tj
2.8177 0 Td
([)Tj
0.83 0.64 0.02 0 k
(4)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2642 0 Td
(5)Tj
0 g
(],)Tj
-34.7865 -1.3039 Td
(release)Tj
2.9026 0 Td
(trophic)Tj
3.1294 0 Td
(factors)Tj
2.9027 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(],)Tj
1.6044 0 Td
(promote)Tj
3.6623 0 Td
(neovascularization)Tj
7.6875 0 Td
([)Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(],)Tj
1.5988 0 Td
(manage)Tj
3.3448 0 Td
(oxidative)Tj
3.8665 0 Td
(stress)Tj
2.3981 0 Td
([)Tj
0.83 0.64 0.02 0 k
(8)Tj
0 g
(])Tj
1.3719 0 Td
(and)Tj
-34.469 -1.2982 Td
(trigger)Tj
2.8799 0 Td
(an)Tj
1.2019 0 Td
(anti-inflammatory)Tj
7.6082 0 Td
(response)Tj
3.736 0 Td
([)Tj
0.83 0.64 0.02 0 k
(9)Tj
0 g
(].)Tj
1.5987 0 Td
(MSCs)Tj
2.6136 0 Td
(are)Tj
1.4456 0 Td
(procured)Tj
3.8891 0 Td
(from)Tj
2.2054 0 Td
(live)Tj
1.6157 0 Td
(donors)Tj
3.0387 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(])Tj
1.8539 0 Td
(and)Tj
1.7291 0 Td
(can)Tj
-35.4158 -1.2983 Td
(be)Tj
1.1508 0 Td
(both)Tj
2.0579 0 Td
(efficiently)Tj
4.1499 0 Td
(expanded)Tj
/F10 1 Tf
4.0876 0 Td
[()1()]TJ
1.0771 0 Td
[()-13()15()3()]TJ
/F6 1 Tf
1.8199 0 Td
([)Tj
0.83 0.64 0.02 0 k
(11)Tj
0 g
(],)Tj
2.0749 0 Td
(and)Tj
1.7291 0 Td
(transplanted)Tj
5.2328 0 Td
(without)Tj
3.3278 0 Td
(previous)Tj
3.651 0 Td
(conditioning)Tj
5.3971 0 Td
(of)Tj
-35.7559 -1.3039 Td
(the)Tj
1.4683 0 Td
(patients)Tj
3.3675 0 Td
(as)Tj
1.0148 0 Td
(opposed)Tj
3.583 0 Td
(to)Tj
1.0261 0 Td
(total)Tj
2.0013 0 Td
(bone)Tj
2.2053 0 Td
(marrow)Tj
3.4072 0 Td
(or)Tj
1.0999 0 Td
(hematopoietic)Tj
5.93 0 Td
(stem)Tj
2.126 0 Td
(cell)Tj
1.559 0 Td
(transplantation)Tj
6.3326 0 Td
([)Tj
0.83 0.64 0.02 0 k
(12)Tj
0 g
(].)Tj
-33.9248 -1.2983 Td
(Several)Tj
3.05 0 Td
(pre-clinical)Tj
4.7395 0 Td
(and)Tj
1.7291 0 Td
(clinical)Tj
3.0784 0 Td
(studies)Tj
2.9877 0 Td
(have)Tj
2.058 0 Td
(previously)Tj
4.3483 0 Td
(reported)Tj
3.6623 0 Td
(that)Tj
1.7802 0 Td
(autologous)Tj
4.5978 0 Td
(or)Tj
1.0998 0 Td
(alloge-)Tj
-34.3273 -1.2982 Td
(neic)Tj
1.8821 0 Td
(MSCs)Tj
2.6136 0 Td
(from)Tj
2.2053 0 Td
(different)Tj
3.6567 0 Td
(sources)Tj
3.1918 0 Td
(are)Tj
1.4513 0 Td
(safe)Tj
1.7235 0 Td
(and)Tj
1.7291 0 Td
(therapeutic)Tj
4.7338 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(treatment)Tj
4.1386 0 Td
(of)Tj
1.0148 0 Td
(chronic)Tj
3.2881 0 Td
(wounds)Tj
-34.1345 -1.304 Td
([)Tj
0.83 0.64 0.02 0 k
(13)Tj
0 g
(],)Tj
2.0749 0 Td
(diabetic)Tj
3.3675 0 Td
(foot)Tj
1.8199 0 Td
(ulcers)Tj
2.5738 0 Td
([)Tj
0.83 0.64 0.02 0 k
(14)Tj
0 g
(],)Tj
2.075 0 Td
(pressure)Tj
3.5773 0 Td
(ulcers)Tj
2.5738 0 Td
([)Tj
0.83 0.64 0.02 0 k
(15)Tj
0 g
(],)Tj
2.0806 0 Td
(burn)Tj
2.1713 0 Td
(injuries)Tj
3.2429 0 Td
([)Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7404 0 Td
(17)Tj
0 g
(],)Tj
1.7348 0 Td
(surgical)Tj
3.3165 0 Td
(wounds)Tj
3.3732 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
-35.7219 -1.2982 Td
(19)Tj
0 g
(],)Tj
1.7347 0 Td
(limb)Tj
2.058 0 Td
(ischemia)Tj
3.7474 0 Td
([)Tj
0.83 0.64 0.02 0 k
(20)Tj
0 g
(],)Tj
2.0749 0 Td
(and)Tj
1.7291 0 Td
(radiation)Tj
3.8778 0 Td
(burns)Tj
2.5342 0 Td
([)Tj
0.83 0.64 0.02 0 k
(21)Tj
0 g
(].)Tj
2.0749 0 Td
(These)Tj
2.5682 0 Td
(studies)Tj
2.9877 0 Td
(indicate)Tj
3.4072 0 Td
(that)Tj
1.7801 0 Td
(wounds)Tj
3.3789 0 Td
(treated)Tj
-33.9531 -1.2983 Td
(with)Tj
1.9955 0 Td
(MSCs)Tj
2.6136 0 Td
(show)Tj
2.3017 0 Td
(a)Tj
0.6519 0 Td
(qualitative)Tj
4.3767 0 Td
(improvement)Tj
5.6693 0 Td
(in)Tj
1.0374 0 Td
(histological)Tj
4.7679 0 Td
(characteristics.)Tj
6.1341 0 Td
(Specifically,)Tj
4.9096 0 Td
(they)Tj
-34.4577 -1.2983 Td
(report)Tj
2.7099 0 Td
(superior)Tj
3.5659 0 Td
(rete)Tj
1.7348 0 Td
(ridge)Tj
2.2734 0 Td
(architecture,)Tj
5.2384 0 Td
(multi-layered)Tj
5.6069 0 Td
(structure,)Tj
4.0478 0 Td
(improved)Tj
4.1102 0 Td
(dermal-epidermal)Tj
-29.2873 -1.3039 Td
(junction)Tj
3.5943 0 Td
(and)Tj
1.7348 0 Td
(the)Tj
1.4683 0 Td
(formation)Tj
4.2576 0 Td
(of)Tj
1.0148 0 Td
(new)Tj
1.8765 0 Td
(skin)Tj
1.8936 0 Td
(appendage)Tj
4.5127 0 Td
(structures,)Tj
4.4107 0 Td
(such)Tj
2.0579 0 Td
(as)Tj
1.0148 0 Td
(hair)Tj
1.8198 0 Td
(follicles)Tj
3.2315 0 Td
(and)Tj
1.7291 0 Td
(seba-)Tj
-34.6164 -1.2982 Td
(ceous)Tj
2.4604 0 Td
(glands)Tj
2.8063 0 Td
([)Tj
0.83 0.64 0.02 0 k
(22)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(26)Tj
0 g
(].)Tj
-4.0705 -1.2983 Td
(Even)Tj
2.2166 0 Td
(though)Tj
3.0784 0 Td
(the)Tj
1.4684 0 Td
(mechanisms)Tj
5.2044 0 Td
(by)Tj
1.1792 0 Td
(which)Tj
2.6532 0 Td
(MSCs)Tj
2.6135 0 Td
(ameliorate)Tj
4.4447 0 Td
(skin)Tj
1.8935 0 Td
(damage)Tj
3.3222 0 Td
(have)Tj
2.058 0 Td
(been)Tj
2.1259 0 Td
(a)Tj
0.652 0 Td
(subject)Tj
-34.1062 -1.3039 Td
(of)Tj
1.0147 0 Td
(debate)Tj
2.8347 0 Td
(for)Tj
1.3833 0 Td
(years,)Tj
2.4888 0 Td
(two)Tj
1.7121 0 Td
(theories)Tj
3.3959 0 Td
(may)Tj
1.9332 0 Td
(currently)Tj
3.8834 0 Td
(explain)Tj
3.1238 0 Td
(MSC)Tj
2.2507 0 Td
(therapeutic)Tj
4.7338 0 Td
(effects:)Tj
2.948 0 Td
(bioactive)Tj
3.8041 0 Td
(solu-)Tj
-35.5065 -1.2983 Td
(ble)Tj
1.3946 0 Td
(factor)Tj
2.5455 0 Td
(production)Tj
4.7111 0 Td
(\(growth)Tj
3.4129 0 Td
(factors,)Tj
3.1295 0 Td
(cytokines)Tj
4.0024 0 Td
(and)Tj
1.7292 0 Td
(specific)Tj
3.1918 0 Td
(proteins\))Tj
3.8551 0 Td
(or)Tj
1.0941 0 Td
(MSC)Tj
2.2564 0 Td
(differentiation)Tj
-31.3226 -1.2983 Td
(into)Tj
1.8425 0 Td
(dermal)Tj
3.0387 0 Td
(and)Tj
1.7291 0 Td
(epidermal)Tj
4.2519 0 Td
(cells)Tj
1.9219 0 Td
([)Tj
0.83 0.64 0.02 0 k
(27)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(28)Tj
0 g
(].)Tj
1.7348 0 Td
(Nevertheless,)Tj
5.4992 0 Td
(it)Tj
0.7823 0 Td
(is)Tj
0.8504 0 Td
(still)Tj
1.6384 0 Td
(controversial)Tj
5.4369 0 Td
(whether)Tj
3.4752 0 Td
(MSCs)Tj
-33.9361 -1.3039 Td
(can)Tj
1.627 0 Td
(contribute)Tj
4.388 0 Td
(significantly)Tj
5.091 0 Td
(to)Tj
1.0262 0 Td
(the)Tj
1.4683 0 Td
(regeneration)Tj
5.3007 0 Td
(of)Tj
1.0148 0 Td
(injured)Tj
3.1465 0 Td
(skin)Tj
1.8935 0 Td
(via)Tj
1.372 0 Td
(tissue)Tj
2.4604 0 Td
(specific)Tj
3.1918 0 Td
(differentia-)Tj
-31.9802 -1.2982 Td
(tion.)Tj
2.0636 0 Td
(For)Tj
1.627 0 Td
(instance,)Tj
3.7531 0 Td
(Wu)Tj
/F10 1 Tf
1.7121 0 Td
[()8()]TJ
0.9071 0 Td
[()11()]TJ
/F6 1 Tf
(.)Tj
1.1678 0 Td
(used)Tj
2.0637 0 Td
(an)Tj
1.2018 0 Td
(excisional)Tj
4.1613 0 Td
(wound)Tj
3.016 0 Td
(model)Tj
2.7439 0 Td
(in)Tj
1.0375 0 Td
(normal)Tj
3.1464 0 Td
(and)Tj
1.7292 0 Td
(diabetic)Tj
3.3675 0 Td
(mice)Tj
2.1543 0 Td
(to)Tj
-35.8523 -1.2983 Td
(prove)Tj
2.4944 0 Td
(that)Tj
1.7745 0 Td
(only)Tj
1.9786 0 Td
(a)Tj
0.6519 0 Td
(small)Tj
2.3301 0 Td
(percentage)Tj
4.5467 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(MSCs)Tj
2.6135 0 Td
(that)Tj
1.7801 0 Td
(migrate)Tj
3.2996 0 Td
(to)Tj
1.0261 0 Td
(injury)Tj
2.6419 0 Td
(sites)Tj
1.9332 0 Td
(in)Tj
1.0375 0 Td
(response)Tj
3.7303 0 Td
(to)Tj
1.0262 0 Td
(che-)Tj
-35.3478 -1.3039 Td
(motactic)Tj
3.6906 0 Td
(signals)Tj
2.9027 0 Td
(become)Tj
3.3222 0 Td
(incorporated)Tj
5.4198 0 Td
(and)Tj
1.7291 0 Td
(survive)Tj
3.0784 0 Td
(within)Tj
2.812 0 Td
(wounded)Tj
3.9684 0 Td
(tissue)Tj
2.4605 0 Td
([)Tj
0.83 0.64 0.02 0 k
(29)Tj
0 g
(].)Tj
2.0749 0 Td
(Likewise,)Tj
3.9062 0 Td
(other)Tj
-35.3648 -1.2983 Td
(studies)Tj
2.9876 0 Td
(have)Tj
2.058 0 Td
(revealed)Tj
3.5263 0 Td
(that)Tj
1.7744 0 Td
(transplanted)Tj
5.2328 0 Td
(MSCs)Tj
2.6078 0 Td
(do)Tj
1.2586 0 Td
(not)Tj
1.5704 0 Td
(need)Tj
2.143 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1509 0 Td
(close)Tj
2.1826 0 Td
(to)Tj
1.0262 0 Td
(the)Tj
1.4683 0 Td
(damaged)Tj
3.8494 0 Td
(site)Tj
1.5704 0 Td
(to)Tj
-35.4328 -1.2982 Td
(promote)Tj
3.6623 0 Td
(wound)Tj
3.016 0 Td
(repair)Tj
2.6022 0 Td
(and)Tj
1.7348 0 Td
(functional)Tj
4.3086 0 Td
(recovery)Tj
3.6454 0 Td
([)Tj
0.83 0.64 0.02 0 k
(30)Tj
0 g
(].)Tj
-17.7731 -1.2983 Td
(Considering)Tj
5.1703 0 Td
(these)Tj
2.2564 0 Td
(previous)Tj
3.651 0 Td
(findings,)Tj
3.719 0 Td
(we)Tj
1.3266 0 Td
(compare)Tj
3.7134 0 Td
(the)Tj
1.474 0 Td
(beneficial)Tj
4.0478 0 Td
(effects)Tj
2.7213 0 Td
(of)Tj
1.0148 0 Td
(mouse)Tj
2.863 0 Td
(bone)Tj
2.2053 0 Td
(mar-)Tj
-35.3591 -1.3039 Td
(row-derived)Tj
5.125 0 Td
(allogeneic)Tj
4.2065 0 Td
(MSCs)Tj
2.6136 0 Td
(\(allo-mBM-MSCs\))Tj
7.7158 0 Td
(and)Tj
1.7348 0 Td
(their)Tj
2.109 0 Td
(acelullar)Tj
3.5716 0 Td
(derivatives)Tj
4.5014 0 Td
(\(allo-acd-)Tj
-31.5777 -1.2983 Td
(mMSCs\))Tj
3.77 0 Td
(to)Tj
1.0261 0 Td
(cutaneous)Tj
4.269 0 Td
(wound)Tj
3.016 0 Td
(healing)Tj
3.1351 0 Td
(in)Tj
1.0318 0 Td
(a)Tj
0.6577 0 Td
(full)Tj
1.525 0 Td
(thickness)Tj
3.9288 0 Td
(excisional)Tj
4.1612 0 Td
(wound)Tj
3.0161 0 Td
(model)Tj
2.7439 0 Td
(in)Tj
1.0375 0 Td
(diabetic)Tj
-33.3182 -1.2983 Td
(mice)Tj
2.1543 0 Td
([)Tj
0.83 0.64 0.02 0 k
(31)Tj
0 g
(].)Tj
2.0749 0 Td
(Allo-mBM-MSCs)Tj
7.2907 0 Td
(or)Tj
1.0941 0 Td
(their)Tj
2.109 0 Td
(allo-acd-mMSCs)Tj
6.9562 0 Td
(were)Tj
2.1203 0 Td
(injected)Tj
3.3902 0 Td
(into)Tj
1.8368 0 Td
(Non-Obese)Tj
4.8246 0 Td
(Diabetic)Tj
-33.8511 -1.3039 Td
(\(NOD\))Tj
3.118 0 Td
(mice.)Tj
2.3811 0 Td
(Wound)Tj
3.2939 0 Td
(healing)Tj
3.1351 0 Td
(was)Tj
1.6951 0 Td
(assessed)Tj
3.4752 0 Td
(macroscopically)Tj
6.6557 0 Td
(every)Tj
2.3471 0 Td
(two)Tj
1.7121 0 Td
(days)Tj
1.9956 0 Td
(in)Tj
1.0375 0 Td
(terms)Tj
2.4888 0 Td
(of)Tj
1.0148 0 Td
(wound)Tj
-34.35 -1.2982 Td
(closure,)Tj
3.2995 0 Td
(and)Tj
1.7291 0 Td
(microscopically)Tj
6.4856 0 Td
(after)Tj
2.0353 0 Td
(16)Tj
1.1678 0 Td
(days)Tj
1.9956 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4627 0 Td
(injection)Tj
3.7587 0 Td
(\(reepithelialization,)Tj
7.9653 0 Td
(dermoepidermal)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 323.4897 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Bone)Tj
2.5157 0 Td
(marrow)Tj
3.5008 0 Td
(mesenchy)Tj
4.4859 0 Td
(mal)Tj
1.8071 0 Td
(stromal)Tj
3.4441 0 Td
(cell)Tj
1.6866 0 Td
(derivati)Tj
3.1536 0 Td
(ves)Tj
1.7575 0 Td
(in)Tj
0.978 0 Td
(skin)Tj
1.963 0 Td
(wound)Tj
3.111 0 Td
(healing)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01775)Tj
4.089 0 Td
(33)Tj
0 g
2.0906 0 Td
(June)Tj
2.3528 0 Td
(8,)Tj
1.0417 0 Td
(2017)Tj
35.5113 0 Td
(2)Tj
0.7654 0 Td
(/)Tj
0.496 0 Td
(17)Tj
/F7 1 Tf
-0.025 Tc
-66.402 84.0904 Td
(Competing)Tj
4.3795 0 Td
(interests)Tj
3.3307 0 Td
(:)Tj
/F8 1 Tf
0.4819 0 Td
(The)Tj
1.5875 0 Td
(authors)Tj
3.0401 0 Td
(have)Tj
1.963 0 Td
(declared)Tj
-14.7827 -1.3748 Td
(that)Tj
1.6228 0 Td
(no)Tj
1.1693 0 Td
(competing)Tj
4.1599 0 Td
(interests)Tj
ET
endstream
endobj
46 0 obj
<>stream
endstream
endobj
47 0 obj
<>stream
endstream
endobj
48 0 obj
<>stream
endstream
endobj
49 0 obj
<>stream
endstream
endobj
50 0 obj
<>stream
endstream
endobj
51 0 obj
<>stream
endstream
endobj
52 0 obj
<>stream
endstream
endobj
53 0 obj
<>stream
endstream
endobj
54 0 obj
<>stream
endstream
endobj
55 0 obj
<>stream
endstream
endobj
56 0 obj
<>stream
endstream
endobj
57 0 obj
<>stream
endstream
endobj
58 0 obj
<>stream
endstream
endobj
59 0 obj
<>stream
endstream
endobj
60 0 obj
<>stream
endstream
endobj
61 0 obj
<>stream
endstream
endobj
62 0 obj
<>stream
endstream
endobj
63 0 obj
<>stream
endstream
endobj
64 0 obj
<>stream
endstream
endobj
65 0 obj
<>stream
endstream
endobj
66 0 obj
<>stream
endstream
endobj
67 0 obj
<>stream
endstream
endobj
68 0 obj
<>stream
endstream
endobj
69 0 obj
<>stream
endstream
endobj
70 0 obj
<>stream
endstream
endobj
71 0 obj
<>stream
endstream
endobj
72 0 obj
<>stream
endstream
endobj
73 0 obj
<>stream
endstream
endobj
74 0 obj
<>stream
BT
10.3394 82.7156 Td
(exist.)Tj
ET
Q
endstream
endobj
75 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 78 0 R/Contents 79 0 R/TrimBox[0 0 612 792]>>
endobj
76 0 obj
<>
endobj
80 0 obj
<>
endobj
81 0 obj
<>stream
%!PS-AdobeFont-1.0
%%This font is a conversion from Helvetica-Oblique with the following copyright notice:
%Copyright (c) 1985, 1987, 1989, 1990, 1997, 1998, 1999 Adobe Systems Incorporated. All Rights Reserved.Helvetica is a trademark of Linotype-Hell AG and/or its subsidiaries.
11 dict begin
/FontName /Helvetica-Oblique def
/FontType 1 def
/FontBBox {-166 -218 1114 770} readonly def
/FontMatrix [0.001 0 0 0.001 0 0] readonly def
/PaintType 0 def
/FontInfo 8 dict dup begin
/FullName (Helvetica-Oblique) readonly def
/BaseFontName (Helvetica-Oblique) def
/Notice (Copyright \(c\) 1985, 1987, 1989, 1990, 1997, 1998, 1999 Adobe Systems Incorporated. All Rights Reserved.Helvetica is a trademark of Linotype-Hell AG and/or its subsidiaries.) readonly def
end def
/Encoding 256 array
0 1 255 {1 index exch /.notdef put} for
dup 32 /space put
dup 33 /exclam put
dup 34 /quotedbl put
dup 35 /numbersign put
dup 36 /dollar put
dup 37 /percent put
dup 38 /ampersand put
dup 39 /quoteright put
dup 40 /parenleft put
dup 41 /parenright put
dup 42 /asterisk put
dup 43 /plus put
dup 44 /comma put
dup 45 /hyphen put
dup 46 /period put
dup 47 /slash put
dup 48 /zero put
dup 49 /one put
dup 50 /two put
dup 51 /three put
dup 52 /four put
dup 53 /five put
dup 54 /six put
dup 55 /seven put
dup 56 /eight put
dup 57 /nine put
dup 58 /colon put
dup 59 /semicolon put
dup 60 /less put
dup 61 /equal put
dup 62 /greater put
dup 63 /question put
dup 64 /at put
dup 65 /A put
dup 66 /B put
dup 67 /C put
dup 68 /D put
dup 69 /E put
dup 70 /F put
dup 71 /G put
dup 72 /H put
dup 73 /I put
dup 74 /J put
dup 75 /K put
dup 76 /L put
dup 77 /M put
dup 78 /N put
dup 79 /O put
dup 80 /P put
dup 81 /Q put
dup 82 /R put
dup 83 /S put
dup 84 /T put
dup 85 /U put
dup 86 /V put
dup 87 /W put
dup 88 /X put
dup 89 /Y put
dup 90 /Z put
dup 91 /bracketleft put
dup 92 /backslash put
dup 93 /bracketright put
dup 94 /asciicircum put
dup 95 /underscore put
dup 96 /quoteleft put
dup 97 /a put
dup 98 /b put
dup 99 /c put
dup 100 /d put
dup 101 /e put
dup 102 /f put
dup 103 /g put
dup 104 /h put
dup 105 /i put
dup 106 /j put
dup 107 /k put
dup 108 /l put
dup 109 /m put
dup 110 /n put
dup 111 /o put
dup 112 /p put
dup 113 /q put
dup 114 /r put
dup 115 /s put
dup 116 /t put
dup 117 /u put
dup 118 /v put
dup 119 /w put
dup 120 /x put
dup 121 /y put
dup 122 /z put
dup 123 /braceleft put
dup 124 /bar put
dup 125 /braceright put
dup 126 /asciitilde put
dup 161 /exclamdown put
dup 162 /cent put
dup 163 /sterling put
dup 164 /fraction put
dup 165 /yen put
dup 166 /florin put
dup 167 /section put
dup 168 /currency put
dup 169 /quotesingle put
dup 170 /quotedblleft put
dup 171 /guillemotleft put
dup 172 /guilsinglleft put
dup 173 /guilsinglright put
dup 174 /fi put
dup 175 /fl put
dup 177 /endash put
dup 178 /dagger put
dup 179 /daggerdbl put
dup 180 /periodcentered put
dup 182 /paragraph put
dup 183 /bullet put
dup 184 /quotesinglbase put
dup 185 /quotedblbase put
dup 186 /quotedblright put
dup 187 /guillemotright put
dup 188 /ellipsis put
dup 189 /perthousand put
dup 191 /questiondown put
dup 193 /grave put
dup 194 /acute put
dup 195 /circumflex put
dup 196 /tilde put
dup 197 /macron put
dup 198 /breve put
dup 199 /dotaccent put
dup 200 /dieresis put
dup 202 /ring put
dup 203 /cedilla put
dup 205 /hungarumlaut put
dup 206 /ogonek put
dup 207 /caron put
dup 208 /emdash put
dup 225 /AE put
dup 227 /ordfeminine put
dup 232 /Lslash put
dup 233 /Oslash put
dup 234 /OE put
dup 235 /ordmasculine put
dup 241 /ae put
dup 245 /dotlessi put
dup 248 /lslash put
dup 249 /oslash put
dup 250 /oe put
dup 251 /germandbls put
readonly def
currentdict end
currentfile eexec
M#1H5 J6o\&rtS(#v\0\V7Fe༙OYx5-cY9^%Y6
(efIOldN"wȰ;)UƽoFg/rvV$JS8_oc@
o9-eGJp}[Do]mN=4*{ܯq=eU^t6¤)wRfxpc@X$UČc@:p:20eַl&^
ZXs/ 1# PGhjtUDA@tZ.nr[
,
"LvJLVguˏrF.Cv
\Fջo. ϛo9aѯxyNh <Іi@qlZz}g2tMag"j e,Ѥ5,[LPE5>ޤfȿB҆}_f☷?QrQYr$#h)[
Y#)793imTV9b#j2-<\ (IlUWwm5q\ѳewY j.Q5ˈZ]7{dEq"2T@cQ)Dso;_H6[l]Y6*'ɾ_I3ajJle>/:y{\M40lD/]K(09u[5