CELL JOURNALYakhteh Vol 14 No 1 Spring 201239 - PDF document

1 CELL JOURNAL(Yakhteh), Vol 14, No 1, Spr
CELL JOURNAL(Yakhteh), Vol 14, No 1, Spring 201239 !"#$%"&'(#)*#+&!,-..#-./#0)."#1-22),#+'2)3-4#+'"3#Cells on Sciatic Nerve Injury in Rat: A Comparison of Func-tional Recovery !"#$!%&!'()(*#+, -,.*#/*#+0(%1!1#2!'(345!%4*#6(,7,1**#8&9:;!:#=!&#x-20.;(4(4*#6(,7,*#+9(!""!1#?!&#x-20.;(4#@9&#x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orresponding Address: P.O.Box: 14155-6183, Department of Anatomy, Cellular and Molecular Research Center, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, IranEmail: mehr_bakhtiyari@yahoo.comK0-04M01P#/.Q8E%Q/R..*#8--0E301P#.SQT-3Q/R..AbstractT&I0-34M0P#Transplantation of bone marrow stromal cells (BMSCs) or Schwann cells (SCs) can facilitate axonal regeneration in peripheral nerve injuries. The aim of this study was to compare the effects of transplantation of BMSCs and SCs on functional recovery after injury to the sciatic nerve in the rat.+!30%4!:)#!C1#+03(91)P !"#$%&"'()'*%+'!#,-"*'&',*.$/",01-#"+,-'"2%&#,*"*,#&"3!456/"5789:88";"='*'"1&'0/"&#x-19.;饢?@A&",!0"@A&"='*'".1-#1*'0/",!0"@A&"='*'".B!C*+'0"=%#$",!#%"@D88",!#%EB0FG"H,#&"='*'"*,!0B+-F"0%I%0'0"%!#B":";*B1)&"3!4J"%!"',.$";*B1)K"DL".B!#*B-";*B1)K"&%-%.B!"#1E'"C--'0"=%#$"CE*%!";'-"=%#$B1#"#$'".'--&/"5L"&#x-19.;饢?@A&";*B1)K"&%-%.B!"#1E'"C--'0"=%#$"CE*%!";'-"&''0'0"=%#$"&#x-19.;饢?@A&",!0":L"@A&";*B1)K"&%-%.B!"#1E'"C--'0"=%#$"CE*%!";'-"&''0'0"=%#$"@A&G"M$'"-'N#"&.%,#%."!'*I'"=,&"'()B&'0/","D8"++"segment removed, and a silicone tube interposed into this nerve gap. BMSCs and SCs were separately transplanted into the gap in the two experimental groups and ='*'"-,E'-'0"=%#$",!#%"&#x-19.;饢*0O",!0"P% "*'&)'.#%I'-FG"QN#'*"D5"=''R&"'-'.#*B)$F&%B-B;%.,-"and functional assessments were performed and analyzed by one-way analysis of variance (ANOVA).K0)D:3)P Electrophysiological and functional assessments showed a significant dif-ference between the experimental groups compared with the control group. Electro-physiological measures were significantly better in the SCs transplantation group .B+),*'0"=%#$"#$'"&#x-19.;饢?@A&"#*',#+'!#";*B1)"3)S8G87G"T1!.#%B!,-",&&'&&+'!#&"showed no statistically significant difference between the BMSCs and SCs groups 3)S8G87GJ9C-:D)49CP#Although both BMSCs and SCs have the potential to produce functional recovery after injury to the sciatic nerve in rats, electrophysiological evaluation con-firms that the improvement after SCs transplantation is greater than that after BM-SCs transplantation.Keywords: Bone Marrow Stromal Cells, Schwann Cells, Transplantation, Peripheral Nerve, RegenerationCell Journal(Yakhteh), Vol 14, No 1, Spring 2012, Pages: 39-46 J43!349CP#$!%&!'()(# *#2!('34!%4#+*#�=!(4(4#8*#�@9(!3!04#+?*#+0(14(+*#A(904# *#+!C)9D%4#A*#F9D)0G#2*#64%(!I!34#H*#+9%!14#=*# (4%"9(!""!14#+,#?(0#U;;0-3)#9;#)-(V!CC#!C1#&9C0#"!%%9V#)3%9"!:#)30"#-0::)#9C#)-4!34-#C0%M0#4CID%5#4C#%!3P#8#-9"E!%4)9C#9;#;DC-349C!:#%0-9M0%5,#J0::#@,#/R./W#.OX.YP#BZ[O\, Original Article CELL JOURNAL(Yakhteh), Vol 14, No 1, Spring 201240Comparison of Functional Recovery of SCs and BMSCs Introduction !"#$%!"&'()!"*!("!+!)!"&,#-)(#.(&)(#/$-",&),(0'#)#0&'($"-1'!/2(3%!($!"#$%!"&'()!"*!(.4.,!/(5 678(%&.(the potential to regenerate nerve cells, and peripheral nerve injury has been successfully repaired using various procedures such as nerve autograft, and nerve guidance tubes (1). In peripheral nerve injury one of the problems is suturing nerve ends when the resulting gap is too long (2). The nerve ends can be bridged with a nerve autograft to provide guidance for the regenerating nerves, but for

2 a larger nerve trauma, a '-)+!"(+"&9,(#
a larger nerve trauma, a '-)+!"(+"&9,(#.("!:;#"!=(&)($.9;鈠%!)(,%!(+"&9,(#.(,%#))!"(than the injured nerve, the transplantation of a bundle -9()!"*!(?1!".(#.("!:;#"!2(@!0&;.!(,%#.($"-0!;"!("!:;#"!.(&('&"+!(+"&9,(9"-/(&(%!&',%4()!"*!=(.!).-"4(&)(/-,-"(!.,";0,#-)(/&4(-00;"(&,(,%!(-)-"(.#,!(5A=(B82Axonal regeneration in a peripheral nerve injury needs extrinsic factors that promote growth, and supply guidance to the target. To overcome these problems, a variety of nerve guide tubes have been used to facilitate cell transplantation. The aims of cellular transplantation include: a. bridging the gap, b. providing a suitable environment to induce axonal regeneration, and c. promoting neovascu-'&"#C&,#-)2(D#99!"!),($"-0!(%&*!(1!!)(&$$'#!(to improve regeneration of peripheral nerves. One of those is the seeding of cells into the nerve guide ,;1!(5E=(BFG82@-)!(/&""-─(.,"-/&'(0!''.(5@H7I.8(%&*!(,%!(&1#'ity to differentiate into different cell lines such as oste-oblasts, cartilage, fat, ligament, muscle, and neurons 5J=(K8=(&)(,-(0-),"#1;,!(,-(,%!(!L$"!..#-)(-9(/&)4(04,-M#)!.=(&)(0!'';'&"(9&0,-".(5N=(EO82(P,(%&.(1!!)(.;++!.,!(,%&,(@H7I.(#/$'&),!($.9;鍠#,%#)()!"*!(+"&9,.(.4),%!.#C!()!;"-,"-$%#0(9&0,-".(&)(!L,"&0!'';'&"(/&trix components which play an important role in the survival and proliferation of axons, and Schwann cells 5EE82(@H7I.(0&)(#/$"-*!(*&.0;'&"#C&,#-)('!&#)+(,-(#)Q;"!(,#..;!("!$&#"(5G=(ER82(3%;.(@H7I.(,"&).$'&)tation may result in recovery of the peripheral nerve &9,!"(#)Q;"4(5EE=(EA82Another cell type used for the repair of periph-eral nerve injures is the Schwann cells (SCs). SCs and their basal lamina are crucial components in the environment through which regenerating ax-ons grow to reach their peripheral targets. SCs can myelinate and produce physical support for axonal $.9;鍠+"-,%($.9;鍠%!)(,%!4(&"!(#)Q;"!(5EB82(7I.(-9(&+!($!"#$%!"&'()!"*!.($"-'#9!"&,!=(%!'$(#)S&//&,-"4(#)?',"&,#)+(0!''.(,-("!/-*!((&)(;$("!+;'&,!(,"-$%#0(9&0,-".(.;0%(&.(#).;'#)F'#M!(&#x-79.;饴+"-,%(factor (IGF), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), and laminin leading to axonal growth promoting. It can be inferred from this evidence that SCs transplantation may also promote recovery in the case of peripheral )!"*!(#)Q;"4(5ET=(EG82Our aim in this study was to compare the impact -9(1-,%(0!''(,4$!.(5@H7I(&)(7I8(-)($!"#$%!"&'(nerve recovery as this has not been compared un-der similar conditions previously.Materials and MethodsAnimals P)(,%#.(.,;=(/&'!(U#.,&"("&,.(5)VRB=(RTOFAOO(+8(ѥ.;5!"!(-1,&#)!(9"-/( &.,!;"(P).,#,;,!=(3!%"&)=(P"&)2(All animals had free access to laboratory chow, &)(,&$(&#x-52.;饠&,!"2(W&,.(&#x-52.;饠!"!("&)((#),-(A(+"-;$.(5)VK(#)(!&0%(+"-;$8X(E2(0-),"-'(+"-;$Y(R2(@H7I.(,"&).$'&),&,#-)(+"-;$Y(A2(7I.(,"&).$'&),&tion group. All procedures in this study, including the use of animals, were approved by the Research I-;)0#'(-9(3!%"&)(Z)#*!".#,4(-9(H!(70#!)0!.((Tehran, Iran), Ethics Committee on Animal Ex-periments whose guidelines are in agreement with ,%-.!(-9(,%!(6&,#-)&'(P).,#,;,!.(-9([!&',%(9-"(,%!(use of live animals.Bone marrow stromal cells cultureP.-'&,!($"!$&"&,#-)(-9(@H7I.(&#x-128;&#x.995;&.($!"9-"/!(&00-")(,-(,%!(/!,%-((14(\C#C#(!,(&'2(5EJ82(@"#!S4("&,.(&#x-670;!"!(M#''!(&#x-238;&#x.007;#,%(&)(-*!"(-9(M!,&/#)(&)(9!/;".(&)(,#1#&.(&#x-123;&#x.989;!"!((out. The marrow was then extruded with 10 ml -9(D;'100-].(H-(^&+'!(H!(5DH^H8(57#+/&(\'(&)(0;',;"!(#)(DH^H(.;$$'!/!),!(&#x-59.;饓#,%(ET_(9!,&'(1-*#)!(.!";/(5`@78(57#+/&(\'(R(/H(aF+';,&/#)!(57#+/&(\'(&)(EOO(/+b/'(M&)&/40#)!(57#+/&(\'(#)0;1&,!(&,(AJcI=(%;/#(NT_=(&)(Id(T_2(\9,!"(BK(%-;".=(,%!()-)&)(0!''.(&#x%!"!;&#x,-63;&#x.994;!"!("!/-*!(14("!$'&0#)+(,%!(/!(@H7I.(&#x#;/2;&#x-123;&#x.002;!"!(.;10;',;"!(9-;"(,#/!.(&)(?)&''4(;.!(#)(,%!(3.9;鞀9-''-#)+(!L$!"#ments.Schwann cells cultureFor the culture of SCs sciatic nerve was ob-tained ;)(&.!$,#0(0-)).2(W&,.(&#x#,#-;
.00;锰!"!(M#''!( CELL JOURNAL(Yakhteh), Vol 14, No 1, Spring 201241 Zarbakhsh et al.and their sciatic nerves were dissected bilaterally &)($'&0!(&,(BcI(#),-([&)M].(1;99!"!(.&',(.-';,#-)(5[@778(.;$$'!/!),!(.9;鍀#,%(EOO(Zb/'($!)#0#'lin (Si

3 gma Aldrich) and 100µg/ml streptomycin (
gma Aldrich) and 100µg/ml streptomycin (Sigma Aldrich). The epineurium and connective tissue were removed under a microscope. The sci-&,#0()!"*!.(.9;鍀!"!(,%!)(0;,(#),-(RFA(//(9"&+/!),.(&)((;.#)+((5E2RT(Zb/'8(57#+/&(\'(&)(0-''&+!)&.!(5O2OT_8(57#+/&(\'(9-"(GFK(%-;".(&,(AJcI2(3%!(,#..;!(#)(,%#.(.-';,#-)(&#x"#0%;艐&.(,"#,;"&,!(#)(&( &.,!;"($#$!,,!(&$$"-L#/&,!'4(ten times and was then incubated overnight at AJcI(#)(T_(Id. The following day the explants were dissociated by gentle trituration. The mixture was then centrifuged at 10("$/(9-"(ET(/#);,!.(at which point the supernatant was removed. The 0!''.(&#x-119;&#x.002;!"!("!.;.$!)(#)(DH^D(/!(0-),&#)#)+(EO_(`@7=(ReH(9-".M-'#)(57#+/&(\'(EOO(Zb/'($!)#0#''#)(&)(EOO(e+b/'(.,"!$,-/40#)=(&)(.00;㐰!"!($'&0!(#)(AT(//($!,"#((I!''.(&#x#.%!;&#x.27.;H䀀!"!(#)0;1&,!(&,(AJcI(#)(T_(Id, and the culture me-(&#x#;/-;Ĵ.;0&.(0%&)+!(!*!"4(BK(%-;".2(\9,!"(B((in primary culture, cytosine arabinoside (Ara-C) 57#+/&(\'(&#x"#0%;-89;&#x.001;怀&.(&(,-(,%!(0;',;"!(,-(&(?nal concentration of 10FT(H=(9-"(&($!"#-(-9(A((3%#.(&#x&4.2;─&.("!$'&0!(&#x-154;&#x.998;#,%(DH^H(0-),&#)#)+(EO_(`@7=(&)(A(('&,!"(,%!(\"&FI(,"!&,/!),(&#x&4.-;.0;Р&.("!$!&,!(I!''.(Ɉ.;饙!"!(,%!)(/&#),&#)!(#)(DH^H(H.9;霰#,%(EO_(`@7=(R/H(aF+';,&/#)!=(EOO(Zb/'($!)#0#''#)=(EOO(e+b/'(.,"!$,-/40#)=(&)(R(eH(9-".M-'#)2(\9,!"(,%!(0;',;"!.("!&0%!(0-)S;!)04=(,%!4(&#x-126;&#x.007;!"!(rinsed three times with phosphate buffered saline 5 @78=(&)(( #,%(O2RT_(,"4$.#)(57#+/&(\'(&)(E/H(^D3\(9-"(T(/#);,!.(&,(AJcI=(&)(.;10;',;"!(&,(&()(-9(TfEO cells/cm. 3%!(7I.(&#x!.#,;-16;�.99;怀!"!(#)(#)('#*#)+(0;',;"!.(-)(,%!(basis of cell soma and nuclear morphology using $%&.!(0-),"&.,(/#0"-.0-$42(P)(?L!(0;',;"!=(,%!4(&#x-121;&#x.001;!"!(#)(14(#//;)-04,-0%!/#0&'('&1!'#)+(9-"(7EOO($"-,!#)(5EK82Transplantation procedureW&,.(&#x-123;!"!(&)!.,%!,#C!(14(#),"&($!"#,-)!&'(#)Q!0,#-)(-9(&(0-/1#)&,#-)(-9(M!,&/#)(5KO(/+bM+8=(&)(L4'&C#)!(5EO(/+bM+82(\9,!"(.M#)(#)0#.#-)(,%!(.0#&,#0(nerve was exposed using a muscle splitting inci-.#-)2(Z)(&)(-$!"&,#)+(/#0"-.0-$!(,%!('!9,(.0#&,#0(nerve was exposed at the mid-thigh, and a 10 mm segment of the nerve was severed and removed. A 12 mm silicone tube (1 mm inner diameter, 2 mm outer diameter) was interposed into this nerve gap 5EN82(@-,%($"-L#/&'(&)((!)(-9(,%!()!"*!(were anchored into the conduit with 10-0 nylon .;,;"!2(3%!(.#'#0-)!(,;1!(#)(,%!(@H7I.(+"-;$(&#x.-11;.99;倀&.(?''!(.99;匐#,%(?1"#)(+!'(.!!(.99;匐#,%(TOO=OOO(@H7I.=(.99;匐%#'!(#)(,%!(7I.(+"-;$(#,(.99;匐&.(?''!(&#x-9.9;隇#,%(?1"#)(+!'(.!!(&#x-128;&#x.998;#,%(TOO=OOO(7I.=(&)(,%!(0-),"-'(+"-;$(&#x-130;&#x.004;#,%(?1"#)(+!'(&#x-130;&#x.004;#,%-;,(0!''.2(`#)&''4(,%!(.M#)(&#x-130;&#x.004;&.(�.;,;"!(((Immunohistochemistry of bone marrow stro-mal cells@H7I.(�!"!('&1!'!(&#x-190;&#x.002;#,%(&(A(e+b/'(@"-/-)(5@"(57#+/&=(\'(.-';,#-)(&(,-(,%!(#)0;1&,#-)(/!(A(($"#-"(,-(transplantation. After transplantation, the sections &#x&4.-;Ņ.;p!"!(#)0;1&,!(#)(TO_(9-"/&/#(5H!"0M=(g!"/&)48=(Rf77I(57,&)(7-(I#,"&,!X(O2AH(6&I'=(&)(O2OAH(7-(I#,"&,!8(&,(GTcI(9-"(R(%-;".=(&#x#;/-;ĸ.; &.%!(9-"(EO(/#);,!.( .0;Ԁ#,%(Rf77I(&,("--/(,!/$!"&,;"!(,%!)(#)0;1&,!(#)(RH([I'(5H!"0M=(g!"/&)48(&,(AJcI(9-"(AO(/#);,!.2(3%!4(&#x-197;&#x.007;!"!(,%!)("#).!(#)(O2EH(@-"#0(\0#(5H!"0M=(g!"/&)48(9-"(EO(/#)=(&#x-65.;餴&.%!(#)( @7=(&)(#)0;1&,!(0.0;ƀ#,%(/-;.!(&),#F@"(/-)-0'-)&'(&),#1-(57#+/&(\'(&,(BcI(-*!")#+%,2\9,!"("#).#)+(A(,#/!.(#)( @7(9-"(EO(/#);,!.=(,%!(.!0,#-).(&#x"#0%;艉&#x.998;!"!(#)0;1&,!(-*!")#+%,(#)(,%!((&,(BcI(&#x&"M-;ĸ.;P#,%("%-)(0-)Q;+&,!(.!0-)(&),#1-(5EX(EOO82(3%!4(-10;.99;䀀!"!(,%!)(-10;.99;䀀&.%!(#)( @7=(covered with a coverslip, and were studied under S;-"!.0!)0!(/#0"-.0-$!(5d'4/$;.(\hJO8(5RO82Immunocytochemistry of Schwann cells7I.(&#x-104;&#x.997;!"!(#)(14(#//;)-04,-0%!/#0&'(labeling for S100 protein. SCs were washed with O2E(H( @7=(?L!(9-"(ET(/#);,!.(#)(B_($&"&9-"/&'($!"/!&1#'#C!(9-"(AO(/#);,!.(&#x-117;&#x.994;#,%(O2E(H( @7(0-),&#)#)+(O2A_(3"#,-)Fh=(&)(E_()-"mal goat serum, and incubated with rabbit anti-7EOO(&),#1-(5H!"0M=(g!"/&)48(9-"(GO(/#);,!(&,(AJcI2(\9,!"(-14;
.99;耀

4 &.%!.(#)( @7=(7I.(-14;
.99;耀!"!
&.%!.(#)( @7=(7I.(-14;
.99;耀!"!(#)0;1&,!(in secondary antibody, goat anti-rabbit cyanine A2EKF'&1!''!(P+g(5EXROO=(H!"0M(g!"/&)48=(9-"(AO(minute at room temperature. Following additional $.9;鍠&.%!.=(7I.(0;',;"!.($.9;鍠!"!(-1.!"*!(;)(&(S;-"!.0!),(/#0"-.0-$!(5d'4/$;.(\hJO8(5RE82Histochemistry of Schwann cells7I.(&#x!"-3; .00;㈀!"!('&1!'!(;.#)+(,%!(S;-"!.0!),('#$-$%#'#0( CELL JOURNAL(Yakhteh), Vol 14, No 1, Spring 201242Comparison of Functional Recovery of SCs and BMSCs ,"&0!"(E=E]F#-0,&!04'FA=A=A]=A]F,!,"&/!,%4'#)-0&"1-04&)#)!($!"0%'-"&,!(5D#P8(57#+/&=(Aldrich) prior to transplantation. For labeling, EfEO(0!''.b/'(&#x-24.;餶!"!("!.;.$!)!(#)(DH^H(&)(Te'b/'(D#P(─&.(&!2(\9,!"(#)0;1&,#-)(9-"(RO(/#);,!&,(AJcI(&#x-24.;饐#,%(T_(%;/##9#!(Id, the 0!''.(&#x-24.;餶!"!(0!),"#9;+!(9-"(T(/#);,!(&)(&#x-24.;餶&.%!(,─#0!(─#,%( @72(3%!4(─!"!(,%!)("!.;.$!)!(#)( @7(9-"(,"&).$'&),&,#-)2(\9,!"(,"&).$'&),&,#-)(9"-C!)(.!0,#-).(─!"!($"!$&"!(&)(,%!('&1!'!(cells were detected using fluorescent micros-0-$4(5d'4/$;.(\hJO8(5RR82Electrophysiological study3─!'*!(─!!M.(&9,!"(,"&).$'&),&,#-)=(,%!("&,.(─!"!(&)!.,%!,#C!(#),"&($!"#,-)!&''4(&#x-104;&#x.004;#,%(M!,&/#)!(5KO(/+bM+8(&)(L'4'&C#)!(5EO(/+bM+8(&)(,%!(.0#&,#0(nerves were exposed. Electric stimulation (dura-,#-)(-9(O2E(/.=(#),!).#,4(-9(R2A(/\8(&#x-130;&#x.004;&.(&$$'#!(to the proximal site of the injured nerve. The com-pound muscle action potential was recorded in the gastrocnemius with a needle electrode and a refer-!)0!(0&$(!'!0,"-(#).!",!(&,(,%!(M)!!(Q-#),2(3%!(stainless steel needle used as the ground electrode &#x-74.;I&.(#).!",!(#),-(,%!(,&#'(.M#)2(3%!(&"!&(-9(,%!("!0-"(/;.0'!("!.$-).!(5/if/.8=(&)(,%!(&/$'#tude were calculated as these can be considered to "!S!0,(,%!(&/-;),(-9(&0,#*&,!((E=(RA82(Functional assessmentFunctional evaluation of the sciatic nerve regen-eration was expressed by the sciatic function index 57`P82(3&#x?1!";&#x.5E3;退!'*!(&#x?1!";&#x.5E3;退!!M.(&9,!"(.;"+!"4=(,%!("&,.(%#)(9!!,($.9;鍠!"!(#$$!(#)(#)M(&)(,%!("&,.($.9;鈠!"!(&''-$.9;鈠!(,-($.9;鍠&'M(through a plastic tunnel so that the footprints could be recorded on paper loaded onto the bottom of the tunnel. The distance between the third toe ant heel 5 a8=(?".,(&)(?9,%(,-!(5378=(&)(.!0-)(&)(9-;",%(,-!(5P378($.9;陀&.(/!&.;"!(-)(,%!(!L$!"#/!),&'(.#!(5^ a=(ETS, and EITS, respectively), and the contra lateral )-"/&'(.#!(56 a=(637=(&)(6P37=("!.$!0,#*!'482(3%!(7`P($.9;鍠&.(0&'0;'&,!(&.(9-''-$.9;鈠.X(7`PVFAK2Af(5^ aF6 a8b6 ajEON2Tf(5^37F6378b637jEA2Af(5^P37F6P378b6P37FK2K2(P)(+!)!"&'=(,%!(7`P(-.0#''&,!.(&"-;)(0 for normal nerve function, whereas around -100 SFI "!$"!.!),.(,-,&'(4.9;)0,#-)(5RA82Statistical analyses\''((&#x&,&1;&#x.008;ሀ!"!(&)&'4C!(14(&#x-91.;8-)!F&4(&)&'4.#.(-9(*&"#&)0!(5\6di\8(&#x-91.;89-''-!(14(,%!(3;M!4(,!.,2(Obtained data were presented as means ± standard )(&)(&('!*!'(-9($kO2OT(&#x-141;&#x.005;&.(0-).#(.,&,#.,#0&''4(.#+)#?0&),2ResultsBone marrow stromal cells culture @H7I.(-1,&#)!(9"-/(,%!(9!/;".(&)(,#1#&.(of adult rats comprised heterogeneous groups of cells after seeding and growing in culture plates. After initial plating, the adherent cells exhibited either a small rounded-shape, a spindle-shape or &('&"+!(S&,,!)!(/-"$%-'-+4(5`#+(E\82(H-.,(0!''.(&#x-33.;#+"!(&)(!L%#1#,!(&(?1"-1'&.,F'#M!(/-"$%-'-+4(-)("!&0%#)+(0-)S;!)0!2(3%!(./&''("-;)(0!''.(&(,-(,%!(.;"9&0!(-9(,%!.!(0!''('&4!".(5`#+(E@82(These rounded cells disappeared after repeated $&..&+!=(7.9;限%!"!&.(,%!(?1"-1'&.,F'#M!(0!''.(1!0&/!(!)"#0%!(\,($&..&+!(B(,%!(?1"-1'&.,F'#M!(0!''.(1!came morphologically homogeneous (Fig1C). Fig1: Cultured bone marrow stromal cells. (A) In P0 stage adherent cells exhibited small round, spindle-shaped (ar-rows) (×200). (B) In P2 stage. Most cells grew, and ex- !"!#$%&'"()"*+,#-*!.$&/)(0 )*)123&4 $&,/+**&()56%$%&cells adhered to the surface of these cell layers (arrows) (×200). (C) In P4 stage rounded cells disappeared, and # $&'"()"*+,#-*!.$&7$**,&"$7+/$&/)(0 )*)1!7+**2& )/)1$neous (arrows) (×200). A CELL JOURNAL(Yakhteh), Vol 14, No 1, Spring 201243 Zarbakhsh et al.Characterization of cultured Schwann cellsT

5 he spindle-shaped cellular morphology of
he spindle-shaped cellular morphology of the SCs seen on the culture plate was viable and ,%!"!(�&.()-(.#+)(-9(#)9!0,#-)2(H-.,(-9(,%!(0!''.(were small, elongated, and spindle shaped (Fig. 2A). Fluorescence microscopy showed the SCs were S100 positive cells. In the culture dishes the SCs had a tendency to line up side by side or !)(,-(!)=(&)(9-"/!(#),!"0-))!0,!()!,&#x-24.;餶-"M.(5`#+(R@82 Fig 2: (A) Cultured Schwann cells were small, elongat-ed, and spindle shaped in P2 stage (arrows) (×200). (B) Schwann cells were labeled with anti S100 antibody, and showed a tendency to line up side by side or end to end, and formed interconnected networks (arrow) (×200). Fig 3: The left sciatic nerve was exposed at the mid-thigh, and a 10 mm segment of the nerve was removed. A 12 mm silicone tube was interposed into this nerve gap. Arrows show two heads of the nerve in the silicone tube. Finding from the immunohistochemistry of BM-SCs and histochemistry of SCs P//;)-%#.,-0%!/#.,"4(.%-�.(,%!(@H7I.('&1!'!(─#,%(&),#(@"Z(&.(4!''-$.9;鈠($-#),.(#)(,%!(0"-..(.!0,#-)(-9(.0#&,#0()!"*!(#)(`#+(B\=(&)(%#.,-0%!/#.,"4(.%-$.9;鈠.(,%!(7I.('&1!'!($.9;鍠#,%(D#P(&.(4!''-$.9;鍠($-#),.(&"-;)(,%!(0"-..(.!0,#-)(-9(.0#&,#0()!"*!(#)(`#+(B@2(d,%!"(,#..;!.(-9(,%!(.0#&,#0()!"*!(0"-..(.!0,#-).(&"!("!(5`#+(B(\=(@82(3%!("!.;',.(0-)?"/(,%!($"!.!)0!(&)(*#&1#'#,4(-9(transplanted cells in the silicone tube bridging ,%!(+&$(B($.9;鍠!!M.(&9,!"(,"&).$'&),&,#-)2 Fig 4: Cross-sections of the sciatic nerve, 4 weeks after transplantation of (A) BMSCs labeled with anti BrdU show as yellow points (arrows) (×100). (B) Schwann cells labeled with DiI show as yellow points around the nerve (arrows).ElectrophysiologyResults of the electrophysiology tests comprise amplitude and latency. The mean amplitude in mil-livolts (mV) and the mean of latency in milliseconds #.(.%-�)(#)(?+;"!(T2(3%!(,#/!(0&'#1"&,#-)(1&"(�&.(R(ms and amplitude calibration bar was 10 mV. The .,#/;'&,#-)(#),!).#,4(�&.(R2A(/\(5/#''#&/$!"!8(&)(,%!(;"&,#-)($.9;陀&.(O2E(/.(5`#+(G823%!("!.;',.(.%-$.9;陀!(,%!"!( .99;䁐!"!(.,&,#.,#0&''4(.#+)#?cant differences between the control group and the !L$!"#/!),&'(+"-;$.(5@H7I.(&)(7I.8Y(&)(,%!"!( .99;䁐&.(&(.,&,#.,#0&''4(.#+)#?0&),(#99!"!)0!(1!, .99;æ¡°!!)(@H7I(+"-;$(&)(7I(+"-;$(5$kO2OT8(5`#+(T82 Fig 5: The results of electrophysiology tests of amplitude and *+#$672&, )8$%&# $($&8$($&,#+#!,#!7+**2&,!16!'7+6#&%!99$($67$,&between the control group and the experimental groups (BM-:;,&+6%&:;,= .0;ፀ&+6%&# $($&8+,&+&,#+#!,#!7+**2&,!16!'7+6#&%!99$($67$&"$#8$$6&# $&?@:;&1()50&+6%&:;&1()503&=0AB3BC ABAB CELL JOURNAL(Yakhteh), Vol 14, No 1, Spring 201244Comparison of Functional Recovery of SCs and BMSCs Fig 6: Electrophysiological waves for the control, BMSC and SC groups 12 weeks after surgery. Amplitude and la-tency is shown for each group. The time calibration bar was 2 ms and the amplitude calibration bar was 10 mV. The stim-ulation intensity was 2.3 mA and the duration was 0.1 ms.Functional analysisThe results of SFI showed there were statistically .#+)#?0&),(#99!"!)0!.(1!,　!!)(,%!(0-),"-'(+"-;$(&)(,%!(!L$!"#/!),&'(+"-;$.(5@H7I.(&)(7I.8=(1;,()-(.,&,#.,#0&''4(.#+)#?0&),(#99!"!)0!(　&.(-1.!"*!(1!,0.0;ƀ!!)(,%!(@H7I(+"-;$(&)(7I(+"-;$(5$kO2OT8(5`#+(J82 Fig 7: The results of the sciatic function index (SFI) test , )8$%&# $($&8$($&,#+#!,#!7+**2&,!16!'7+6#&%!99$($67$,&"$tween the control group and the experimental groups (BM-:;,&+6%&:;,"5#&6)&,#+#!,#!7+**2&,!16!'7+6#&%!99$($67$&8+,&)",$(E$%&"$#8$$6&# $&?@:;&1()50&+6%&:;&1()50&=0AB3BC3 Fig 8. Foot print of control, BMSC and SC groups 12 weeks after surgery. Arrow shows walking direction.DiscussionInjuries of peripheral nerves, describe one of the most challenging microsurgical problems. These damages are associated with considerable disabili-ty due to loss of both motor and sensory functions. D!*!'-$/!),(-9(&(%#+%(:;&'#,4("!$'&0!/!),(9-"(auto grafts is needed because the auto graft pro-cedure entails multiple surgeries, loss of function, &)((())((()((((((In this study we compared the effect of trans-$'&),&,#-)(-9(@H7I.(&)(7I.(

6 -)("!0-*!"4(-9("&,(sciatic nerve injury.
-)("!0-*!"4(-9("&,(sciatic nerve injury. Several investigators have &#x-820;.%-)(,%&,(@H7I.(&)(7I.(0&)("!$&#"(#)Q;"4(,-(,%!(.0#&,#0()!"*!(5EE=(EA=(ET=(EG82(&#x-110;[-!*!"=(&.(,%!4(have not compared the results under similar condi-tions, their results are not comparable. Comparing these two methods under identical conditions may '!&(;.(,-()-*!'(0'#)#0&'(&$$"-&0%!.(9-"(;,#'#C#)+(these cells to replace peripheral nerve recovery auto grafts.@!0&;.!(.,!/(0!''.(&"!(#/$-",&),(.!!)(0!''.(for peripheral nerve regeneration, special attention has been given to the development of a rich and &00!..#1'!(0!'';'&"("!.!"*-#"(9-"(,%#.(0!''(,4$!(5RB82(Several studies have showed the potential capabil-#,4(-9(;.#)+(0;',;"!(@H7I.(#)($!"#$%!"&'()!"*!("!+!)!"&,#-)2(@H7I.(0&)($"-/-,!(&L-)&'("!+!)!"&,#-)(#)( 67(5EE=(RT82(@H7I.(0&)(1!(&.$#"&,!(directly from donors and include heterogenous $-$;'&,#-).(-9(0!''.(ɉ.;馀#,%()($'&.,#0#,4(5RB82(D;"#)+($!"#$%!"&'()!"*!("!+!)!"&,#-)(,"-$%#0(9&0tors and supporting substances are essential mol-ecules which play important roles, particularly for ,%!("!+!)!"&,#-)(-9('-)+()!"*!((5EN=(RG82(Researchers have indicated several mechanisms that may result in the promotion of functional im-$"-*!/!),(14(@H7I.2(3%!.!(0!''.(.!0"!,!(/&)4(factors such as neurotrophic factors that induce tissue plasticity, and neuroprotective factors (27). @H7I.(%&*!(,%!(&1#'#,4(,-("!'!&.!()!;"-,"-$%#0(9&0,-".(.;0%(&.Y(6g`=(@D6`=(gD6`=(I63`(&)(VEGF, as well as to produce extracellular matrix $"-,!#).(.;0%(&.Y(0-''&+!)(P=(0-''&+!)(Pi=(?1"-)!0,#)=(&)('&/#)#)(5G=(EE82(3%!"!9-"!(,%!"!(#.(+--(evidence to support the hypothesis that transplan-,&,#-)(-9(@H7I.(/&4("!$&#"($!"#$%!"&'()!"*!(#)Q;"#!.(5EE=(EA82One of the effective cell candidates used in cell transplantation after peripheral nerve injuries are CELL JOURNAL(Yakhteh), Vol 14, No 1, Spring 201245 Zarbakhsh et al.SCs. SCs are essential for the successful improve- !"#$%&$'(%"')$*!+!"!,'#-%".$/!,-01!,')$"!,2!$,!generation occurs mainly through a series of reac-tions produced by activated SCs so that the axons of the proximal nerve stump grow through the dis-tal stump in close contact with the SCs. They pro-duce various trophic factors for regenerating ax-%"3$4567.$8'))!,-'"$*!+!"!,'#-%"$'9#-2'#!3$#1!$:;3$and they supply an ideal trophic milieu for axonal regeneration by secreting growth factors such as; &#x=000;?$&#x=000;@=?$&#x=000;AB=$'"*$�CD45E7.$F"$'**-#-%"?$SCs mediated by immunoglobulin superfamily %)!9G)!3?$)-H!$#1!$"!,2!$9!))$'*1!3-%"$ %)!9G)!?$protein 0, cadherin, and the protocadherins, are - 0%,#'"#$&%,$'(%"')$!)%"+'#-%"$'"*$%,+'"-I!*$sprouting. SCs also produce basal lamina compo-"!"#3?$)-H!$9%))'+!"$FA?$'"*$)' -"-"$#1'#$0)'J$'"$essential role in nerve regeneration. Among the adhesion molecules, laminin is the most potent factor for promoting axonal outgrowth. It thus 3!! 3$)-H!)J$#1'#$#,'"30)'"#'#-%"$%&$:;3$ 'J$')3%$,!0'-,$0!,-01!,')$"!,2!$-"KG,-!3$4L7.8!$9G)#G,!*$'"*$)'M!)!*$#1!$CN:;3$O-#1$C,*P.$The immunohistochemistry process showed that C,*PQ0%3-#-2!$CN:;3$9'"$3G,2-2!$-"$#1!$3-)-9%"!$#GM!$'#$#1!$+'0$'&#!,$R$O!!H3.$S1!$+'0$-3$)%9'#!*$between the ends of the proximal and the distal %&$#1!$"!,2!$�4-+$L7.$S1-3$T"*-"+$-3$9%"3-3#!"9!$O-#1$0,!2-%G3$,!0%,#3$45R?$LU7.$S1!$0,!3!"#$3#G*J$9%"T, !*$#1!$0,!3!"9!$%&$:;3$MJ$G3-"+$'"#-$:VUU$'"#-M%*J$-"$2-#,%?$'"*$9%"T, !*$#1!$2-'M-)-#J$%&$#1!$:;3$MJ$D-F$3#'-"-"+$-"$#1!$3-)-9%"!$#GM!$'#$#1!$+'0?$'&#!,$R$O!!H3.$S1-3$,!3G)#$')3%$-3$-"$'+,!! !"#$O-#1$0,!2-%G3$O%,H3$455?$LU7.F"$#1-3$3#G*J?$O!$31%O!*$#1!$M!"!T#$%&$,!0'-,-"+$VU$ $"!,2!$*!&!9#3$MJ$G3-"+$CN:;3$'"*$SCs separately, as evidenced by electrophysiology #!3#3$$-"$#1!$+'3#,%9"! -G3$ G39)!?$'"*$O')H-"+$behavior as measured by foot print analysis. The results of the electrophysiology tests showed there O!,!$3#'#-3#-9'))J$3-+"-T9'"#$*-&&!,!"9!3$M!#O!!"$the control group and the experimental groups 4CN:;3$'"*$:;37.$:% !$0,!2-%G3)J$,!0%,#!*$*'#'$3G00%,#$%G,$T"*-"+3$4VV?$5V?$5R?$LV7W$B2!"$#1%G+1$#1!$T"*-"+3$%&$!)!9#,%01J3-%)%+J$#!3#3$%&$#1!$:;3$#,'"30)'"#!*$+,%G0$O!,!$3-+"-T9'"#)J$1-+1!,$#1'"$#1!$CN:;3$#,'"30)'"#!*$+,%G0?$#1!$!(0!,- !"#$had not been compare

7 d under similar conditions. The better r
d under similar conditions. The better recovery in the SC group was probably due to the direct and essential role of SCs in the regeneration and recreation of axonal bridges. The results of the SFI tests showed there were statis-#-9'))J$3-+"-T9'"#$*-&&!,!"9!3$M!#O!!"$#1!$9%"#,%)$+,%G0$'"*$#1!$!(0!,- !"#')$+,%G03$4CN:;3$'"*$:;37.$S1!3!$T"*-"+3$9%"T, $#1%3!$*%9G !"#!*$0,!2-%G3)J$4VV?$L5$Q$LR7W$MG#$#1!$)'9H$%&$'"J$3#'#-3#-9'))J$3-+"-T9'"#$*-&&!,!"9!$%M3!,2!*$M!#O!!"$#1!$CN:;$+,%G0$'"*$:;$+,%G0$-3$"!O$'3$#1!3!$have not previously been compared under similar conditions.X3$,!+',*3$M%#1$9!))$#J0!3$4CN:;$'"*$:;7$1'2!$the ability to release neurotrophic factors such as; &#x=000;?$�CD'"*$�AB=?$'3$O!))$'3$#%$0,%*G9!$!(tracellular matrix proteins such as collagen IV and )' -"-"$4Y?$VV?$LU7?$9% 0',-"+$#1! $G"*!,$3- -)',$conditions could be an important step in the selec-tion of a repair procedure based on the measure of peripheral nerve recovery. ConclusionZG,$,!3G)#3$3G++!3#$#1'#$M%#1$CN:;3$'"*$:;3$have the potential to generate functional recovery of injury to the sciatic nerve of the rat. Electro-physiological evaluation showed that the incorpo-ration of SCs into nerve conduits produced bet-#!,$,!3G)#3$#1'"$#1%3!$%&$CN:;3.$S1!3!$$T"*-"+3$provide greater support for use of SCs instead of CN:;3$&%,$#1!$9)-"-9')$,!0'-,$%&$0!,-01!,')$"!,2!3$damage.AcknowledgmentsThe present study was supported by a grant from S!1,'"$P"-2!,3-#J$%&$N!*-9')$:9-!"9!3?$;!))G)',$'"*$N%)!9G)',$[!3!',91$;!"#!,.$S1!$9,J%3!9#-%"ing process was performed at the anatomy depart- !"#$%&$S',M-'#$N%*',!3$P"-2!,3-#J.$8!$!(0,!33$%G,$*!!0$'00,!9-'#-%"$&%,$D,.$:')!1"-'$'"*$N,3.$BM,'1- -\3$3G00%,#.$S1!,!$-3$"%$9%"]-9#$%&$-"#!,!3#$in this article.References1. Belkas JS, Shoichet MS, Midha R. Peripheral nerve re- !"!#$%&'"(%)#'* )( *&+$",!(%*-!./(0!*#'1(2!./(34456(37839:(;3/(&#x;=;7;/27;耀&11!.&(?/(0!#@!( #$A%&" /(B1&"(C1$.%(D*# /(;EF56(;;8;9:(;4;G/3. Ide C. Peripheral nerve regeneration. Neurosci Res. ;EE76(3(5/(Ishikawa N, Suzuki Y, Dezawa M, Kataoka K, Ohta M, Cho H, et al. Peripheral nerve regeneration by transplantation of BMSC-derived Schwann cells as chitosan gel sponge .,$AA'1+./(H(I&'J!+(࠹:;&#x;4;=;&#x;3;/;➀$%!#(2!.(K/(344E6(FE859:(;;;F=;;35/ CELL JOURNAL(Yakhteh), Vol 14, No 1, Spring 201246Comparison of Functional Recovery of SCs and BMSCs 5. Dezawa M. Future views and challenges to the peripheral nerve regeneration by cell based therapy. Rinsho Shinkei- $L*/(344(;9:(FMM=FME/6. Fan W, Crawford R, Xiao Y. The ratio of VEGF/PEDF ex-pression in bone marrow mesenchymal stem cells regulates "!'@$.,*1$#&N$%&'"/(O&AA!#!"%&$%&'"/(34;;6(F;8G9:(;F;=;E;/7. Sanches-Ramos J, Song S, Cardozo-Pelaez F, Hazzi C, Stedeford T, Willing A, et al. Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol. 34446(;75839:(35M=38. Woodbury D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal cells differentiate into "!*#'"./(H(0!*#'.,&(2!./(34446(7;859:(G75=GM4/9. Dormady SP, Bashayan O, Dougherty R, Zhang XM, Basch RS. Immortalized multipotential mesenchymal cells and the hematopoietic microenvironment. J Hematother D%!J(B!11(2!./(344;6(;48;9:(;3;4/(Bhagavati S, Xu W. Isolationand enrichment of skeletal muscle progenitor cells from mouse bone marrow. Bio-,)!J(I&'P)Q.(2!.(B'JJ*"/(34456(G;F8;9:(;;E=;35/11. Chen CJ, Ou YC, Liao SL, Chen WY, Chen SY, Wu CW, et al. Transplantation of bone marrow stromal cells for pe-#&P)!#$1("!#@!(#!P$&#/(RSP(0!*#'1/(344M6(3458;9:(55G=5(;3/(Marzban M, Bakhtiary M, Mehdizadeh M, Joghataei MT, Khoei S, PirhajatiMahabadi V, et al. Intravenous injection of human umbilical cord matrix stem cell (Wharton jelly stem cell) provides functional recovery in a rat model of traumatic brain injury. Cell Journal(Yakhteh)/(34;46(;38;9:(FM=E7/(13. Braga-Silva J, Gehlen D, Roman JA, Menta C, Atkinson EA, Machado DC, et al. Bone marrow and platelet-rich plasma stem cells effects on nervous regeneration and functional recovery in an acute defect model of rats’ pe-#&P)!#$1("!#@!/(K,%$(T#%'P(I#$./(34476(;58(;5/(Wakao S, Hayashi T, Kitada M, Kohama M, Matsue D, Teramoto N, et al. Lon

8 g-term observation of auto-cell transpla
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