CN116640188B - 一种宫内膜干细胞在子宫韧带修复中的应用 - Google Patents
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Abstract
本发明涉及一种宫内膜干细胞在子宫韧带修复中的应用。本发明通过筛选获得了能够促进子宫内膜干细胞和子宫韧带成纤维细胞Fibulin‑5高表达特性的多肽CF‑A3,所述多肽具有较好的安全性,同时将该多肽与子宫内膜干细胞和/或子宫韧带成纤维细胞分别或组合一起使用后,能够有效的促进Fibulin‑5高表达进而子宫韧带修复。将所述组分制备成为药物组合物后能够更加便利的使用。
Description
技术领域
本申请涉及生物领域,具体的,涉及一种宫内膜干细胞在子宫韧带修复中的应用。
背景技术
子宫内膜是一个高度再生的组织,在月经周期中进行动态的,周期性的生长、分化、脱落和再生。子宫内膜作为胚胎发育的土壤,,其再生对胚胎的着床和妊娠的维持至关重要。由于频繁的宫腔操作史,感染及部分药物的使用,子宫内膜损伤的发生逐渐增多,特别是子宫肌瘤剔除,子宫内膜炎或反复流产后清宫等导致的子宫内膜基底层破坏,造成子宫内膜重度损伤,再生修复困难,常引起子宫前后壁之间纤维瘢痕和粘连的形成,临床上可表现为月经减少,闭经,不孕,习惯性流产,早产和胎盘异常等。有研究表明,近三分之二的胚胎种植失败是由于内膜因素所致,而宫腔粘连又是内膜所致不孕中最主要,最难解决的一个病因,因此,对于重度子宫内膜损伤的治疗是临床上亟待解决的问题。
干细胞可定向分化为不同胚层的功能细胞,自体移植可修复受损组织、改善组织器官功能。目前在各系统疾病尤其是退行性疾病和器官功能衰竭的治疗中备受重视,被认为是解决这类疾病的新希望。生殖系统疾病多因功能障碍或结构受损导致生殖能力减弱,不同来源的干细胞可通过多种机制改善生殖器官功能,恢复生育能力,已成为目前的研究热点。
很多研究者强调干细胞具有丰富的分泌活性,其发挥作用可能是由于旁分泌因素,这些因素包括不同类型的细胞因子的分泌,如生长因子,抗炎和促炎因子,抗凋亡因子等。体外培养的干细胞可以分泌血管内皮生长因子,肝细胞生长因子,碱性成纤维细胞生长因子,胎盘生长因子,血小板衍生因子等众多与血管新生相关的细胞因子,基于干细胞移植的动物实验证明,干细胞在体内也可以通过分泌并提高组织内的血管生长因子水平,利于血管新生,从而促进缺血组织的修复。移植的干细胞进入损伤部位后可通过自分泌和旁分泌作用产生细胞因子。有研究发现干细胞分泌的外泌体,对抗凋亡基因,和具有上调作用,对促凋亡基因和具有下调作用,从而抑制损伤细胞的凋亡,对组织的修复及再生起到重要作用,当组织发生损伤,血管系统遭到破坏的病理条件下,干细胞对损伤组织分泌的信号如炎性因子立即做出反应,通过分泌血管活性因子,刺激内皮细胞的增殖与分化,招募血管周细胞或血管平滑肌细胞,当组织损伤严重的情况下,内源性的干细胞尚不足以维持内环境的稳态,需借助于移植外源性的干细胞,发挥血管新生的作用,促进组织的修复。
子宫内膜干细胞有上皮和基质两种类型,可能存在于功能层和基底层,并可随月经排出。子宫内膜干细胞在内膜增生修复、组织分化等方面的特性使其受到越来越多的关注。
人子宫内膜干细胞可以在体内产生内膜组织已经在动物模型中得到证实。将人子宫内膜上皮干细胞和MSC接种到免疫缺陷小鼠肾包膜下,可以产生子宫内膜层和肌层组织。在卵巢切除的免疫缺陷小鼠中,再生的内膜有腺样结构、基质及肌层样组织。这种异种移植产生的内膜对模拟人月经周期的雌孕激素产生反应。雌激素能刺激上皮和基质增生,在此基础上给予孕激素则腺体变得弯曲,基质出现蜕膜样变化。而随着孕激素的撤退,一些大的充血囊泡形成,提示月经形成。小鼠子宫内膜上皮祖细胞的数量可能受雌孕激素的调控。把从人子宫内膜分离的SP细胞接种到小鼠肾包膜下也能形成内膜组织,而非SP细胞则不能。这些研究表明,子宫内膜中存在可以体内产生内膜组织的干细胞。子宫内膜间充质干细胞(eMSC):eMSC因其存在位置较其他来源的MSC对于修复盆底脏器更具有优势,且更易方便获取,成为一个有潜力的干细胞来源。在体外诱导eMSC分化为阴道平滑肌细胞(SMC),为eMSC治疗子宫内膜损伤提供了理论基础。将eMSC+纳米纤维网植入模型小鼠皮肤创伤处,可以有效减轻急性炎症反应,促进胞外基质合成、血管生成和抗炎基因表达,形成新的胶原,提示eMSC+纳米纤维网能促进创伤愈合,可以作为治疗子宫内膜损伤的替代性外科结构。
子宫内膜干细胞在体外和体内实验中均显示出具有子宫内膜再生和修复功能,提示其可能在子宫内膜的正常变化周期中发挥着重要作用。随着子宫内膜干细胞研究得到越来越多的关注,子宫内膜MSC的标记物已有报道,并依此发现子宫内膜MSC在子宫内膜功能层和基底层均有分布。目前也证实经血中也存在子宫内膜MSC,且具有多向分化潜能,但是目前,将子宫内膜干细胞用于子宫韧带修复的研究还不够多,提供的可选择的治疗方式也还不够,有待于本领域进一步的研究。
发明内容
本发明克服现有技术的缺陷,提供了一种子宫内膜干细胞在制备子宫韧带修复的药物中的用途。
一方面,研究人员发现子宫内膜干细胞能够在体内分化成为子宫韧带成纤维细胞从而具体的实现子宫韧带修复。
目前研究发现,Fibulin-5是一种钙依赖性弹性蛋白结合蛋白,它在弹性蛋白聚合过程中作为弹性蛋白交联排列的支架来发挥作用,促进弹性纤维的生成。子宫内膜干细胞或者子宫韧带成纤维细胞在高表达Fibulin-5时能够有效的促进子宫韧带修复。
因此,进一步的,本发明首先提供了一种能够促进Fibulin-5高表达特性的多肽CF-A3,该多肽的氨基酸序列如SEQ ID NO:1所示,该多肽是通过筛选获得。该多肽能够促进子宫内膜干细胞以及子宫韧带成纤维细胞中的Fibulin-5高表达,从而实现子宫韧带修复。
本发明提供的多肽CF-A3,还可以采用本领域常规的方式进行修饰,所述修饰能够保持多肽仍然保持相应的活性,或者具有更好的抗消化特性。
通常,通过在一个或多个位置改变选择的分子以生成期望的多样性。选择待改变的位置,从而针对环序列中各独立位置构建文库。合适时,可从选择过程中忽略一个或更多个位置,例如,如果很明显这些位置中不存在不损失活性的突变。
随后变异可以通过随机化获得,在其间原位氨基酸被任何氨基酸或其类似物,天然或合成的,所取代,产生非常大量变体,或者可通过用一个或更多个限定的氨基酸亚系列(subset)取代原位氨基酸,产生数量更有限的变体。
技术人员可以考虑所谓的“保守”氨基酸置换,其通常可以描述为氨基酸置换,在所述氨基酸置换中,氨基酸残基被另一个相似化学结构的氨基酸残基替换,且所述氨基酸置换对多肽的功能、活性或其他生物学性质具有很少影响或基本没有影响。这样的保守氨基酸置换在本领域中是众所周知的,例如,来自WO 04/037999,GB 335768,WO 98/49185,WO00/46383和WO 01/09300;和这样的置换的(优选)类型和/或组合可以基于来自例如WO04/037999或例如WO98/49185和从其中引用的其它参考文献的相关教导中选择。
此类保守置换优选是以下组(a)-(e)中的一个氨基酸被相同组的另一个氨基酸残基置换的置换:(a)小脂肪族,非极性或弱极性残基:Ala,Ser,Thr,Pro和Gly;(b)极性带负电荷的残基及其(不带电荷的)酰胺:Asp,Asn,Glu和Gln;(c)极性带正电荷的残基:His,Arg和Lys;(d)大的脂族,非极性残基:Met,Leu,Ile,Val和Cys;和(e)芳族残基:Phe,Tyr和Trp。特别优选的保守置换如下:Ala至Gly或至Ser;Arg至Lys;Asn至Gln或至His;Asp至Glu;Cys至Ser;Gln至Asn;Glu至Asp;Gly至Ala或至Pro;His至Asn或至Gln;Ile至Leu或至Val;Leu至Ile或至Val;Lys至Arg,至Gln或至Glu;Met至Leu,至Tyr或至Ile;Phe至Met,至Leu或至Tyr;Ser至Thr;Thr至Ser;Trp至Tyr;Tyr至Trp;和/或Phe至Val,至Ile或至Leu。
己经报道了引入这种多样性的各种方法。用于使所选位置突变的方法也是本领域公知的。
进一步的,本发明提供了一种用于治疗子宫韧带损伤修复的药物组合物,所述组合物含有子宫内膜干细胞、子宫韧带成纤维细胞和多肽CF-A3,该多肽的氨基酸序列如SEQID NO:1所示。
进一步的,本发明提供了子宫内膜干细胞、子宫韧带成纤维细胞和多肽CF-A3在制备用于治疗子宫韧带损伤修复的药物组合物中的用途,其中多肽CF-A3的氨基酸序列如SEQID NO:1所示。
进一步的,本发明提供了子宫内膜干细胞和多肽CF-A3在制备用于治疗子宫韧带损伤修复的药物组合物中的用途,其中多肽CF-A3的氨基酸序列如SEQ ID NO:1所示。
进一步的,本发明提供了子宫韧带成纤维细胞和多肽CF-A3在制备用于治疗子宫韧带损伤修复的药物组合物中的用途,其中多肽CF-A3的氨基酸序列如SEQ ID NO:1所示。
更进一步的,本发明提供药物组合物中还含有药学上可接受的载体。
有用的固体载体包括细碎分裂的固体,诸如滑石、粘土、微晶纤维素、硅石、矾土等。有用的液体载体包括水、羟烷类或二醇类或水-醇/二醇掺合剂,其中本发明的多肽可以以有效水平溶解或分散,任选地在无毒表面活性剂的帮助下。可以添加佐剂诸如香味剂和其它抗微生物剂,以将给定用途的特性最优化。得到的液体组合物可以通过吸收衬垫应用,用于浸渍的绷带及其它敷料,或者使用泵型或气溶胶喷雾器喷到感染区域。
进一步的,本发明的药物组合物为片剂、药片、丸剂、胶囊等形式。
所述片剂、药片、丸剂、胶囊等还可以包含下列各项:粘合剂,诸如黄蓍胶、阿拉伯树胶、玉米淀粉或明胶;赋形剂,诸如磷酸二钙;崩解剂,诸如玉米淀粉、马铃薯淀粉、褐藻酸等;润滑剂,诸如硬脂酸镁;并且可以加入甜味剂,诸如蔗糖、果糖、乳糖或阿司帕坦,或者调味剂,诸如薄荷、冬青油、或樱桃调味剂。当单位剂型是胶囊时,除上述类型的物质之外,它还可以包含液体载体,诸如植物油或聚乙二醇。各种其它物质可以作为涂层存在,或者另外修饰所述固体单位剂型的物理形式。例如,片剂、丸剂、或胶囊可以用胶、蜡、紫胶或糖等包被。糖浆或酏剂可以包含本发明的多肽,作为甜味剂的蔗糖或果糖,作为防腐剂的对羟基苯甲酸甲酯和对羟基苯甲酸丙酯类,染料和调味剂诸如樱桃或橙味调味剂。当然,在制备任何单位剂型中所用的任何物质都应该是药物可接受的,并且在所用的量上基本上无毒。另外,本发明的多肽可以结合在持续释放的制剂和装置中。
适于注射或输注的药物剂型可以包括包含活性成分的无菌的水溶液或分散液或者无菌粉剂,其适合即时制备无菌注射或输注溶液或分散体,任选地包封在脂质体中。在所有情形中,在制备和保存条件下,最终剂型必须是无菌的、流动的和稳定的。液体载体或赋形剂可以是溶剂或液体分散介质,例如,其包括水、乙醇、多元醇(例如,甘油、丙二醇、液体聚乙二醇等)、植物油、无毒甘油酯及其适当的混合物。可以保持适当的流动性,例如,通过形成脂质体,在分散剂的情形中通过保持需要的颗粒大小或者通过使用表面活性剂。防止微生物作用可以通过各种抗细菌和抗真菌试剂获得,例如,对羟基苯甲酸酯类、氯代丁醇、苯酚、山梨酸、硫柳汞等。在许多情形中,优选地包括等渗剂,例如,糖、缓冲剂或氯化钠。可注射组合物的延长吸收可以通过在所述组合物中使用延迟吸收剂例如单硬脂酸铝和明胶而获得。
有益效果
本发明通过筛选获得了能够促进子宫内膜干细胞和子宫韧带成纤维细胞Fibulin-5高表达特性的多肽CF-A3,所述多肽具有较好的安全性,同时将该多肽与子宫内膜干细胞和/或子宫韧带成纤维细胞分别或组合一起使用后,能够有效的促进Fibulin-5高表达进而子宫韧带修复。将所述组分制备成为药物组合物后能够更加便利的使用。
附图说明
图1不同多肽在子宫韧带成纤维细胞中促进Fibulin-5表达情况结果图
图2不同浓度的CF-A3对子宫韧带成纤维细胞Fibulin-蛋白的表达影响结果图
具体实施方式
下面将参照附图更详细地描述本发明的具体实施例。虽然附图中显示了本发明的具体实施例,然而应当理解,可以以各种形式实现本发明而不应被这里阐述的实施例所限制。相反,提供这些实施例是为了能够更透彻地理解本发明,并且能够将本发明的范围完整的传达给本领域的技术人员。尽管本文使用了特定的术语,但它们仅用于一般性和描述性的意义,而不是为了限制的目的。除非另有定义,否则本文使用的所有技术和科学术语具有与本公开描述的主题所属领域的普通技术人员通常理解的相同的含义。
实施例1子宫韧带成纤维细胞的制备及鉴定
取未生育SD大鼠,脱颈处死,无菌条件下取大鼠盆底子宫双侧韧带组织,PBS反复冲洗后置入培养皿中,小心剔除周围脂肪组织,无血清HBSS漂洗三遍,吸净培养液,眼科剪将组织剪成约0.25mm3左右的小块,加入0.25%含EDTA的胰酶在5%CO2、37℃,饱和湿度条件下消化3小吋,期间反复吹打。加入含10%胎牛血清的培养基终止消化,1000r/min离心2次,弃上清,用含10%胎牛血清的DMEM培养液悬浮细胞,计数活细胞数,调整细胞密度,接种于50ml塑料培养瓶中,置CO2培养箱内培养。每天观察细胞,每3~4天换液一次,待细胞融合后,正常传代。取第4代大鼠子宫韧带成纤维细胞,进行胶原I型、III型常规免疫组织化学染色鉴定显示,胶原I型、III型均棕色着色呈学阳性表达,显微镜下可见胞体细长,长梭形平行排列,符合成纤维细胞特征,鉴定制备获得了大鼠子宫韧带成纤维细胞。
实施例2子宫韧带成纤维细胞中Fibulin-5高表达促进剂的筛选
将实施例1制备的子宫韧带成纤维细胞用含0.02%EDTA和0.5%胰酶的消化液消化,吹打成细胞悬液计数,调整细胞密度。将细胞以5X103个/孔的密度接种到96孔板中,每孔体积200μl。将培养板置入CO2孵箱中,在37℃、5%CO2条件下培养。将发明人构建的多肽库按照10μg/mL添加到各孔中,培养2d,检测其中Fibulin-蛋白的表达情况,5个复孔重复,取平均值,以不添加多肽的孔作为空白对照。结果如图1所示。
从图1可以看出,CF-A3具有最强的促进Fibulin-5高表达的特性。因此,后续选择该多肽进行后续的细胞内促进Fibulin-5高表达的实验。
实施例3不同浓度的CF-A3对子宫韧带成纤维细胞Fibulin-蛋白的表达影响
将实施例1制备的子宫韧带成纤维细胞用含0.02%EDTA和0.5%胰酶的消化液消化,吹打成细胞悬液计数,调整细胞密度。将细胞以5X103个/孔的密度接种到96孔板中,每孔体积200ul。将培养板置入CO2孵箱中,在37℃、5%CO2条件下培养。将CF-A3按照10μg/mL、100μg/mL、200μg/mL、300μg/mL添加到各孔中,培养2d,检测其中Fibulin-蛋白的表达情况,5个复孔重复,取平均值,以不添加多肽的孔作为空白对照。结果如图2所示。
从图2可以看出,随着CF-A3浓度的增加,促进Fibulin-5高表达的特性越强。但是,在超过200μg/mL浓度之后,促进作用下降。因此,后续选择该多肽浓度为200μg/mL进行后续实验。
实施例4不同浓度的CF-A3对人子宫内膜干细胞的Fibulin-蛋白的表达影响
将购买的人子宫内膜干细胞(货号为CM-H230,武汉普诺赛生命科技有限公司)用含0.02%EDTA和0.5%胰酶的消化液消化,吹打成细胞悬液计数,调整细胞密度。将细胞以5X103个/孔的密度接种到96孔板中,每孔体积200ul。将培养板置入CO2孵箱中,在37℃、5%CO2条件下培养。将CF-A3按照10μg/mL、100μg/mL、200μg/mL、300μg/mL添加到各孔中,培养2d,检测其中Fibulin-蛋白的表达情况,5个复孔重复,取平均值,以不添加多肽的孔作为空白对照。结果如表1所示。
表1不同浓度的CF-A3多肽对人子宫内膜干细胞Fibulin-蛋白的表达影响
*表示与空白对照组相比,差异显著(P<0.05)。
从表1可以看出,随着CF-A3浓度的增加,CF-A3多肽对人子宫内膜干细胞Fibulin-蛋白的表达促进特性越强。这说明,本发明的CF-A3多肽能够有效的用于促进人子宫内膜干细胞Fibulin-蛋白的促进表达。
实施例5CF-A3安全性实验
SD大鼠先分多肽高、低剂量组(分别50μg/cm2、1mg/cm2),PBS溶剂对照组3组,每组再分为完整皮肤组和破损皮肤组,共6组,每组10只,给药8周,1次/d,保鲜膜覆盖,纱布固定,每次接触6h后除去包覆,观察各组大鼠的异常毒性反应(体质量、全身状况)。给药24h后,检查皮肤病理学、血液生化指标、肝肾脾等主要脏器毒性作用情况。
连续给药期间以及给药结束24h后,各组均未出现中毒剂量和中毒表现。皮肤也未发现水肿、红斑等病理状况,皮肤病理学检查鳞状上皮细胞层完整,细胞层次清楚,排列整齐,毛囊结构和腺体形态清晰,未见基底细胞变化、增生出血等其它异常反应。皮下组织未见水肿、炎细胞浸润。血液生化指标正常、肝肾脾等主要脏器均正常。这说明本发明的多肽具有较好的安全性。
实施例6大鼠子宫内膜损伤模型建立及动物实验
未交配9周SD雌性大鼠,5%水合氯醛溶液麻醉6mL/kg,麻醉后取仰卧位。消毒后在下腹正中切口,耻骨联合上2cm,打开腹膜,进入腹腔,轻轻夹出V型子宫。无菌生理盐水纱布保护子宫周围,0号缝合丝线活结结扎子宫两端,结扎力度适中。轻微拉直子宫,1mL注射器针头进入宫腔,平行与子宫纵轴,注射95%乙醇约0.4mL,使子宫呈充盈状态,且保持无液体明显溢出。作用约5min将95%乙醇吸出,生理盐水冲洗宫腔3遍,松解子宫两端结扎线,观察子宫恢复情况。后将左侧子宫轻轻送回,同法处理右侧子宫,后逐层关腹,送至保温箱待其肌张力恢复,送动物房。检测发现宫腔缩小,子宫内膜凸起不明显,子宫内膜上皮呈偏平状或低柱状,子宫内膜变薄、子宫内膜间质腺体数量减少,子宫内膜间质纤维化明显,表明造模成功。
将造模成功的小鼠采用如下分组进行实验:
实验1:宫腔移植人子宫内膜干细胞0.1mL(108个/mL)(货号为CM-H230,武汉普诺赛生命科技有限公司);
实验2:宫腔移植人子宫内膜干细胞0.1mL(108个/mL)(货号为CM-H230,武汉普诺赛生命科技有限公司)和宫腔注射CF-A3多肽500μg;
实验3:宫腔移植实施例1制备的子宫韧带成纤维细胞0.1mL(108个/mL);
实验4:宫腔移植宫腔移植实施例1制备的子宫韧带成纤维细胞0.1mL(108个/mL);和宫腔注射CF-A3多肽500μg;
实验5:宫腔移植人子宫内膜干细胞0.1mL(108个/mL)(货号为CM-H230,武汉普诺赛生命科技有限公司)、实施例1制备的子宫韧带成纤维细胞0.1mL(108个/mL)和宫腔注射CF-A3多肽500μg;
阳性对照组:将0.1ml的水凝胶经原位注射到已损伤的子宫内膜上,水凝胶中包载肝素高亲和性细胞因子的肝素-泊洛沙姆凝胶的质量百分含量为54.9%、氨基化芦荟多糖-甘油醛凝胶的质量百分含量为10%、维生素C的质量百分含量为1%、子宫内膜去细胞基质的质量百分含量为35%。
每组3次给药,间隔5d;第17d处死小鼠,以4μm厚度连续切片,脱蜡水化,苏木精染色5min,1%盐酸酒精分化3s,1%氨水中蓝化3s,伊红溶液染色4min,脱水、透明、中性树胶封片。子宫内膜腺体计数:每张切片随机选取4个不同高倍视野(200×),计腺体数量,取平均值。子宫内膜厚度(100×):通过计算机图像分析系统测量子宫肌层与内膜交界处至宫腔的垂直距离,切片4个象限中子宫内膜的厚度,取平均值。结果如表2所示。
表2各组子宫内膜腺体计数及子宫内膜厚度比较
从表2可以看出,与正常组想比较,模型组的子宫内膜腺体计数显著减少,子宫内膜厚度也是显著减小(P<0.05)。经过各实验组的治疗后,与模型组比较,子宫内膜腺体计数都显著增多,子宫内膜厚度也是显著增加(P<0.05)。从表2可以看出,人子宫内膜干细胞相对于子宫韧带成纤维细胞直接治疗有一定的滞后性,导致效果相比有所差异。单独使用人子宫内膜干细胞相对于子宫韧带成纤维细胞直接治疗有一定的滞后性,导致效果相比有所差异。而与单独使用人子宫内膜干细胞或子宫韧带成纤维细胞相比,分别添加了多肽一起使用后,人子宫内膜干细胞或子宫韧带成纤维细胞均较为显著的提高了相应的治疗效果。特别是多肽与人子宫内膜干细胞和子宫韧带成纤维细胞三者组合使用后,相对于阳性对照组有显著的效果提升,差异有统计学意义。
以上所述仅是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。
最后应说明的是:以上各实施例仅用以说明本发明的技术方案,而非对其限制;尽管参照前述各实施例对本发明进行了详细的说明,但本领域的普通技术人员应当理解:其依然可以对前述各实施例所记载的技术方案进行修改,或者对其中部分或者全部技术特征进行等同替换;而这些修改或者替换,并不使相应技术方案的本质脱离本发明各实施例技术方案的范围。
Claims (8)
1.一种能够促进Fibulin-5高表达特性的多肽CF-A3,该多肽的氨基酸序列如SEQ IDNO:1所示,该多肽能够促进子宫内膜干细胞以及子宫韧带成纤维细胞中的Fibulin-5高表达,从而实现子宫韧带修复。
2.一种用于治疗子宫韧带损伤修复的药物组合物,所述组合物含有子宫内膜干细胞、子宫韧带成纤维细胞和多肽CF-A3,该多肽的氨基酸序列如SEQ ID NO:1所示。
3.子宫内膜干细胞、子宫韧带成纤维细胞和多肽CF-A3在制备用于治疗子宫韧带损伤修复的药物组合物中的用途,其中多肽CF-A3的氨基酸序列如SEQ ID NO:1所示。
4.子宫内膜干细胞和多肽CF-A3在制备用于治疗子宫韧带损伤修复的药物组合物中的用途,其中多肽CF-A3的氨基酸序列如SEQ ID NO:1所示。
5.子宫韧带成纤维细胞和多肽CF-A3在制备用于治疗子宫韧带损伤修复的药物组合物中的用途,其中多肽CF-A3的氨基酸序列如SEQ ID NO:1所示。
6.如权利要求3-5任一所述的用途,其中所述药物组合物中还含有药学上可接受的载体。
7.如权利要求6所述的用途,其特征在于载体是液体载体,包括水、羟烷类或二醇类或水-醇掺合剂。
8.如权利要求7所述的用途,其特征在于药物组合物为注射剂剂型。
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