CN111936174A - 生物工程化的华通氏胶衍生的细胞外基质 - Google Patents
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Abstract
本发明提供了源自脱细胞的华通氏胶基质(DWJM)的生物工程化的细胞外基质模型以及制备和使用它的方法。脱细胞后,DWJM被均化、冷冻,并在模具中被冻干以形成具有基本均匀的孔隙尺寸、孔隙分布和基质组分分布的模制支架,并且可被修剪和成形为任何所需的尺寸。生物工程化的DWJM能够保持所培养细胞的干细胞特性,这在筛选靶向癌症,特别是癌症干细胞群体的化疗药物方面是有用的。生物工程化的DWJM具有类似于骨造血生态位的基质组分,并且可用于扩增和维持造血干细胞以及促进骨再生和修复。
Description
相关申请的引证
本申请要求2018年3月30日提交的美国临时专利申请第62/650,551号的优先权,其内容通过引用整体并入本文。
背景技术
华通氏胶是脐带血管周围的粘液样多孔结缔组织。华通氏胶含有大量蛋白质、糖胺聚糖和生长因子,这使它成为合适的天然支架材料。脱细胞后,华通氏胶产生了多孔、可生物降解且生物相容的无细胞支架,并且保留了其细胞外基质蛋白。然而,由于脱细胞的华通氏胶基质(DWJM)的来源是脐带,所以DWJM的尺寸、厚度、组成和蛋白质分布在每根脐带之间,甚至在每根脐带的不同区域之间变化很大,这使得它难以以一致的方式使用。
本领域需要改进的脱细胞华通氏胶基质构建体。本发明满足了这一需求。
发明内容
在一个方面,本发明提供了多孔基质,其包含中位孔隙尺寸范围为约200μm至约350μm的模制的脱细胞华通氏胶基质(DWJM)。
在一个实施方案中,中位孔隙尺寸范围为约230μm至约330μm。在一个实施方案中,中位孔隙尺寸为约235μm、约275μm、约290μm、约300μm、约310μm、约320μm或约330μm。在一个实施方案中,孔隙尺寸分布不超过中位孔隙尺寸的50%或17%。在一个实施方案中,该基质的体积孔隙率在约80%与95%之间。
在一个实施方案中,所述基质还包含均匀分布的基质组分,所述基质组分选自由以下组成的组:胶原蛋白、纤连蛋白、肌腱蛋白C(TN-C)、原纤蛋白、基膜聚糖蛋白、透明质酸(HA)、多功能蛋白聚糖(versican)、纤维蛋白原γ链、肌球蛋白-9、肌球蛋白-10、paladin、细丝蛋白、纽蛋白、膜突蛋白、骨膜蛋白、层粘连蛋白、踝蛋白-1及其组合。
在一个实施方案中,该基质的纤维蛋白原γ链丰度比在约30与35之间。在一个实施方案中,该基质的肌球蛋白-9丰度比在约10与15之间。在一个实施方案中,该基质的肌球蛋白-10丰度比在约10与15之间。
在一个实施方案中,该基质可被模制或修剪成尺寸适合于细胞培养孔的圆盘形状。在一个实施方案中,该基质还包含至少一个接种细胞的群体。在一个实施方案中,该基质还包含至少一种治疗剂。
在另一方面,本发明提供了制备生物工程化的基质的方法,其包括以下步骤:将脱细胞的华通氏胶基质(DWJM)浸渍在液体介质中;对浸渍的DWJM执行一个或多个均化循环以形成均化的DWJM,每个均化循环包括均化期和休止期;将均化的DWJM成形;将均化的DWJM冷冻;以及将冷冻的DWJM在真空下冻干以形成生物工程化的基质。
在一个实施方案中,液体介质是蒸馏水。在一个实施方案中,对保存在冰上的浸渍的DWJM执行一个或多个均化循环。在一个实施方案中,每个均化周期包括约30秒的均化期和约120秒的休止期。在一个实施方案中,每个均化期包括在浸渍的DWJM中激活分散混合器。在一个实施方案中,执行至少30个均化循环。在一个实施方案中,使用3D打印来对将均化的DWJM成形。在一个实施方案中,使用模具使均化的DWJM成形。在一个实施方案中,在约-80℃与-180℃之间执行冷冻步骤。在一个实施方案中,在约-20℃与-60℃之间、在约0.05毫巴下执行冻干步骤。
在另一方面,本发明提供了促进受试者的骨再生的方法,其包括以下步骤:提供本发明的多孔基质;在该基质中载入一种或多种成骨和血管生成生长因子;以及将该多孔基质植入在受试者的骨缺损处。
在另一方面,本发明提供了培养造血干细胞的方法,其包括将CD34+细胞接种到本发明的多孔基质上的步骤,其中细胞在多孔基质上培养时保持在静止期。在一个实施方案中,接种的CD34+细胞具有巨核细胞谱系偏倚。
在另一方面,本发明提供了癌症模型,其包括本发明的多孔基质和包埋在多孔基质中的癌细胞群体。在一个实施方案中,癌细胞群体表现出癌症干细胞特征。在一个实施方案中,癌细胞群体选自由以下组成的组:白血病、淋巴瘤、骨髓瘤、乳腺癌、前列腺癌、子宫内膜癌、膀胱癌、脑癌、宫颈癌、肺癌、黑色素瘤、宫颈癌、卵巢癌、结直肠癌、胰腺癌、食道癌、肾癌、甲状腺癌、肝癌、子宫癌、软组织肉瘤、骨癌和胃癌。
附图说明
当结合附图阅读时,能更好地理解本发明实施方案的以下详细描述。然而,应该理解,本发明不限于附图中所示的实施方案的精确布置和手段。
图1A至图1D描绘了之前公布的脱细胞华通氏胶基质(DWJM)的表征。(图1A)DWJM的代表性碎片。(图1B)DWJM的切片的H&E染色。(图1C)DWJM的SEM图像。(图1D)DWJM的TEM图像。
图2A和图2B描绘了生物工程化的DWJM。(图2A)冻干后的生物工程化的DWJM片材。(图2B)冻干后的生物工程化的DWJM圆盘的SEM图像(左)。请注意中间图中的孔隙尺寸(31-79μm)和原发性白血病患者细胞在DWJM纤维上的附着(右)。
图3A至图3C描绘了表征生物工程化的DWJM的结果。(图3A)生物工程化的DWJM的切片的SEM图像。(图3B)将生物工程化的DWJM的切片分成三个区域以进行表征。(图3C)表征每个区域的孔隙率和孔隙尺寸的结果(该结果展示了该孔隙率和孔隙尺寸的基本均匀性)。
图4是示出表征图3B所示的生物工程化的DWJM的切片的每个区域中的孔隙尺寸分布的结果的曲线图。
图5是示出图3B所示的生物工程化的DWJM的切片中所有三个区域的平均孔隙尺寸分布的曲线图。
图6A至图6D是示出如通过质谱测定法确定的DWJM的切片与尺寸相当的示例性生物工程化的DWJM的切片之间的较丰富的基质组分的丰度比的图表。
图7A至图7B是示出如通过质谱测定法确定的DWJM的切片与尺寸相当的示例性生物工程化的DWJM的切片之间的不太丰富的基质组分的丰度比的图表。
图8是列出了用于制造生物工程化的DWJM的示例性方法的步骤的流程图。
图9是示出DWJM中处于悬浮状态的原代白血病细胞(左)和处于贴壁状态的白血病细胞(右)的图。预测的触发糖酵解的细胞信号以贴壁状态示出。
具体实施方式
本发明提供了源自脱细胞的华通氏胶基质(DWJM)的生物工程化的细胞外基质模型以及制备和使用它的方法。脱细胞后,DWJM被均化、冷冻,并在模具中被冻干以形成具有基本均匀的孔隙尺寸、孔隙分布和基质组分分布的模制支架,并且可被修剪和成形为任何所需的尺寸。生物工程化的DWJM保持了所培养的细胞的干细胞特性,这对于筛选靶向癌症,特别是癌症干细胞群体的化疗药物是有用的。生物工程化的DWJM具有类似于骨造血生态位的基质组分,并且可用于扩增和维持造血干细胞以及促进骨再生和修复。
定义
应当理解,已经简化了本发明的附图和描述,以阐明与清楚理解本发明相关的元件,同时为了清楚起见,去除了本领域中通常存在的许多其它元件。本领域普通技术人员可以认识到,在实现本发明时,其它元件和/或步骤是期望的和/或需要的。然而,因为此类元件和步骤在本领域中是众公知的,并且因为它们不利于更好地理解本发明,所以本文不提供对此类元件和步骤的论述。本文的公开内容涉及本领域技术人员已知的此类元件和方法的所有此类变化和修改。
除非在别处定义,否则本文使用的所有技术和科学术语具有与本发明所属领域的普通技术人员通常所理解的相同的含义。尽管在本发明的实践或测试中可使用类似于或等同于本文所述的方法和材料的任何方法和材料,但描述了示例性的方法和材料。
如本文中所用,以下每个术语都具有本节中的与其相关的含义。
冠词“一个/种(a)”和“一个/种(an)”在本文中用于指一个或多于一个(即,至少一个)该冠词的语法对象。举例来说,“元素”意味着一个元素或多于一个元素。
如本文中所用的“约”,当指可测量的值,诸如量、持续时间等时,意在包括与规定值相差±20%、±10%、±5%、±1%和±0.1%的变化,因为此类变化是合适的。
术语“细胞”和“细胞群体”可互换使用,并且是指多个细胞,即多于一个细胞。所述群体可以是包含一种细胞类型的纯群体。替代地,所述群体可包含多于一种细胞类型。在本发明中,对细胞群体可包含的细胞类型的数量没有限制。
“分化的”在本文中用于指这样的细胞,该细胞已经达到成熟的终末状态,因此该细胞已经完全发育并表现出生物专化和/或对特定环境和/或功能的适应。通常,分化细胞的特征在于该细胞中编码分化相关蛋白的基因的表达。当细胞被称为“正在分化”时,正如本文中所使用的该术语,该细胞处于正在分化的过程中。
“分化培养基”在本文中用于指这样的含有添加剂或不含添加剂的细胞生长培养基,其使得当在该培养基中孵育时,未完全分化的干细胞、组织来源的成体基质细胞或其它此类祖细胞发育成具有分化细胞的一些或全部特征的细胞。
术语“源自”在本文中用于表示源自指定的来源。
“可扩增性”在本文中用于指细胞增殖,例如,在数量上扩增或在细胞群体的情况下经历群体倍增的能力。
化合物的“有效量”或“治疗有效量”是指足以向施用该化合物的受试者提供有益效果的化合物的量。递送载剂(vehicle)的“有效量”是指足以有效地结合或递送化合物的量。
“细胞外基质”或“基质”是指这样的一种或多种物质,其提供的支持细胞生长的条件与由饲养细胞合成的细胞外基质所提供的条件基本相同。所述基质可提供于衬底上。替代地,一种或多种包含所述基质的组分可以溶液形式提供。
如本文中所用,“生长因子”旨在指以下非限制性因子,包括但不限于生长激素、促红细胞生成素、促血小板生成素、白细胞介素3、白细胞介素6、白细胞介素7、巨噬细胞集落刺激因子、c-kit配体/干细胞因子、骨保护素配体、胰岛素、胰岛素样生长因子、表皮生长因子(EGF)、成纤维细胞生长因子(FGF)、神经生长因子、睫状神经营养因子、血小板衍生生长因子(PDGF)、转化生长因子(TGF-β)、肝细胞生长因子(HGF)和骨形态发生蛋白,其浓度在皮克/ml至毫克/ml的水平之间。
如本文中所用,术语“生长培养基”意指促进细胞生长的培养基。生长培养基一般含有动物血清。在一些情况下,生长培养基可以不含动物血清。
“分离的细胞”是指这样的细胞,该细胞已经与组织或哺乳动物中的自然伴随该分离的细胞的其它组分和/或细胞分离。
如本文中所用,术语“多能(multipotential)”或“多能性(multipotentiality)”意在指干细胞分化为多于一种类型的细胞的能力。
如本文中所用,“多能细胞”定义分化程度较低的细胞,其可产生至少两种不同的(基因型和/或表型上不同的)进一步分化的子代细胞。
术语“前体细胞”、“祖细胞”和“干细胞”在本领域和本文中可互换使用,是指多能或谱系未定的祖细胞,其潜在地能够具有无限数量的有丝分裂来更新其自身或产生将分化成所需细胞类型的子代细胞。与多能干细胞不同,谱系定型的祖细胞一般被认为不能产生许多在表型上彼此不同的细胞类型。相反,祖细胞产生一种或可能两种谱系定型的细胞类型。
“增殖”在本文中用于指类似形式(尤其是细胞的类似形式)的繁殖或扩增。也就是说,增殖包括更多数量的细胞的产生,并且可通过简单地计数细胞数量、测量3H-胸苷在细胞中的掺入等来测量。
“细胞周期的进程或贯穿细胞周期的进程”在本文中用于指细胞籍以准备和/或进入有丝分裂和/或减数分裂的过程。贯穿细胞周期的进程包括贯穿G1期、S期、G2期和M期的进程。
术语“患者”、“受试者”、“个体”等在本文中可互换使用,是指无论在体外还是在原位,都适用于本文所述的方法的任何动物或其细胞。在某些非限制性实施方案中,患者、受试者或个体是人。
贯穿本公开,本发明的各个方面可以以范围格式呈现。应当理解,范围格式的描述仅仅是为了方便和简洁,不应当被解释为对本发明的范围的不灵活的限制。因此,范围的描述应该被认为已明确公开了所有可能的子范围以及该范围内的各个数值。例如,诸如从1至6的范围的描述应该被认为已明确公开了诸如1至3、1至4、1至5、2至4、2至6、3至6等的子范围,以及该范围内的各个数字,例如1、2、2.7、3、4、5、5.3、6,以及其间的任何全部和部分增量。无论范围有多宽,这都适用。
生物工程化的脱细胞华通氏胶基质
本发明涉及生物工程化的脱细胞华通氏胶基质(DWJM)。该生物工程化的DWJM保留了DWJM的3D结构和细胞外基质组成,并提高了孔隙尺寸、孔隙分布和基质组分分布的基本均匀性。
华通氏胶是脐带的凝胶状结缔组织,其主要支持脐带中的血管(图1A至图1D)。它包括丰富的细胞外基质组分,诸如胶原蛋白、纤连蛋白、透明质酸和硫酸化蛋白聚糖,以及许多生长因子,包括胰岛素样生长因子1(IGF-1)、成纤维细胞生长因子(FGF)、转化生长因子β1(TGF-β1)、表皮生长因子(EGF)和血小板衍生生长因子(PDGF)。
本发明的生物工程化的DWJM包含已从脐带分离、脱细胞、均化并在模具中冻干以形成基本均匀的3D基质结构的华通氏胶。该生物工程化的DWJM可具有任何合适的尺寸或形状,所述尺寸或形状可以由所使用的模具的尺寸和形状来确定,或者通过修剪现有的生物工程化的DWJM来确定。例如,可以最初使生物工程化的DWJM形成为薄片,然后将其修剪或切割成更小的块(图2A)或者成形(诸如用活检穿孔器)为圆盘(图2B)。可将具有圆盘形状的生物工程化的DWJM的尺寸调整为适合于多孔板(例如96孔板)的孔,并且能够支持高通量筛选和其它研究。
该生物工程化的DWJM可具有任何合适的孔隙尺寸。例如,孔隙尺寸的直径可在约10μm至1000μm的范围内。在一些实施方案中,生物工程化的DWJM的中位孔隙尺寸在约200μm与350μm之间。在一些实施方案中,中位孔隙尺寸在约230μm与330μm之间。在一些实施方案中,中位孔隙尺寸为约235μm、约275μm、约290μm、约300μm、约310μm、约320μm或约330μm。孔隙尺寸分布的均匀性可被描述为中位孔隙尺寸的某个百分比以内的偏差。在各种实施方案中,孔隙尺寸分布偏离不超过中位孔隙尺寸的50%。在一些实施方案中,孔隙尺寸分布偏离不超过中位孔隙尺寸的17%。
该生物工程化的DWJM可具有任何合适的体积孔隙率。体积孔隙率被定义为材料中的空隙空间的量度。例如,两种不同的生物工程化的DWJM可具有相同的体积尺寸和相同的孔隙尺寸范围,但具有不同的体积孔隙率,其中具有较大体积孔隙率的生物工程化的DWJM具有较多数量的孔,每个孔之间具有较少的基质材料,而具有较小体积孔隙率的生物工程化的DWJM包含较少数量的孔,每个孔之间具有较多的基质材料。在各种实施方案中,该生物工程化的DWJM可具有在约80%与95%之间的体积孔隙率。
如上所述,华通氏胶是从脐带中收获的,因此其组成在每根脐带之间,甚至在每根脐带的不同区域之间是不同的。该生物工程化的DWJM包含均匀分布的基质组分,包括但不限于:胶原蛋白、纤连蛋白、肌腱蛋白C(TN-C)、原纤蛋白、基膜聚糖蛋白、透明质酸(HA)、多功能蛋白聚糖、纤维蛋白原γ链、肌球蛋白-9、肌球蛋白-10、paladin、细丝蛋白、纽蛋白、膜突蛋白、骨膜蛋白、层粘连蛋白和踝蛋白-1。
制备生物工程化的DWJM的方法
本发明还涉及制备本文别处所述的生物工程化的DWJM的方法。现参考图8,描绘了制备生物工程化的基质的示例性方法100。方法100始于步骤102,其中将脱细胞的华通氏胶基质(DWJM)浸渍在液体介质中。在步骤104中,对浸渍的DWJM执行一个或多个均化循环以形成均化的DWJM,其中每个均化循环包括均化期和休止期。在步骤106中,使均化的DWJM成形。在步骤108中,将均化的DWJM冷冻。在步骤110中,将冷冻的DWJM在真空下冻干以形成生物工程的基质。
华通氏胶基质可以以任何合适的方式制备和脱细胞以形成DWJM(参见美国专利申请公布第2011/0165676号和美国专利第9,814,802号,其各自通过引用整体并入本文)。例如,在各种实施方案中,华通氏胶基质可通过从脐带中完全分离、通过在血管结构完整的情况下分离,或通过使用整个脐带来制备。脐带可来自任何合适的来源,包括但不限于人和其它胎盘哺乳动物,诸如灵长类动物和有蹄类动物。可通过一个或多个渗透休克循环(Osmotic shock cycle)对华通氏胶基质进行脱细胞。渗透休克循环一般涉及华通氏胶基质交替暴露于高渗溶液和低渗溶液。示例性渗透休克循环包括在含有氯化钠、甘露醇、氯化镁和氯化钾的高渗盐溶液与含有含0.005%Triton X-100的双蒸水的低渗溶液之间交替,在每种溶液中孵育1小时。在一些实施方案中,低渗溶液孵育可以在离心下进行。进一步的处理步骤可包括去垢剂洗涤、酶消化和有机溶剂提取,以及接着使用离子交换珠去除所有残留物质。
可将DWJM浸渍在任何合适的介质诸如蒸馏水中。液体介质的量可以控制所得生物工程化的DWJM的孔隙尺寸,其中较高比例的脱细胞组织可产生具有较小孔隙尺寸的生物工程化的DWJM,而较低比例的脱细胞组织可产生具有较大孔隙尺寸的生物工程化的DWJM。例如,每1mL液体介质0.5g脱细胞组织的比例能够产生孔隙尺寸在约30μm与80μm之间的生物工程化的DWJM。
液体介质浸渍使得DWJM能够被一致地均化。每个均化循环包括均化期和休止期以允许DWJM溶液冷却。均化步骤可在冰上进行,以提高冷却速度。均化期可在约10秒与1分钟之间,休止期可在约30秒与5分钟之间。在一些实施方案中,均化期为约30秒,休止期为约120秒。在各种实施方案中,可以进行介于约10个与100个之间的均化循环。
可以以任何合适的方式使均化的DWJM成形。例如,在一些实施方案中,均化的DWJM可被3D打印成任何所需的尺寸和形状。均化的DWJM可被3D打印成具有任何合适的支持结构,诸如可使用公知的后处理步骤去除的外壳或框架。在其它实施方案中,可通过加载到任何尺寸的模具中来使均化的DWJM成形。在一些实施方案中,选择具有较大的非特定形状的模具,以使得可针对任何所需的形状对最终模制的DWJM进行修剪和重新调整尺寸。将成形的均化的DWJM在-80℃或更低的温度下冷冻至少8小时。然后将冷冻的DWJM在约-20℃和-60℃的温度下,在约0.01毫巴至0.1毫巴的真空下冻干至少8小时。
在各种实施方案中,生物工程化的DWJM可用灭菌步骤进行处理。灭菌步骤可以应用任何合适的灭菌方法。例如,在制造生物工程化的DWJM的过程中的任何阶段,DWJM组分可以用辐射(例如,γ辐射、x射线辐射、紫外线灭菌和电子束处理)、气态甲醛、二氧化碳、臭氧、环氧乙烷、过乙酸、乙醇、过氧化氢等处理。
在一些实施方案中,可用一种或多种添加剂来增强生物工程化的DWJM。该添加剂可被混合到均质的DWJM样品中并且可促进细胞系的贴壁和生长。例如,所述一种或多种添加剂可包括一种或多种另外的细胞外基质材料和/或天然存在的细胞外基质材料的共混物,所述天然存在的细胞外基质材料包括但不限于胶原蛋白、纤维蛋白、纤维蛋白原、凝血酶、弹性蛋白、层粘连蛋白、纤连蛋白、玻连蛋白、透明质酸、4-硫酸软骨素、6-硫酸软骨素、硫酸皮肤素、硫酸肝素、维沙帕汀(VP12)、肝素和硫酸角质素、蛋白聚糖及其组合。一些可能有益的胶原蛋白包括但不限于I型、II型、III型、IV型、V型、VI型、VII型、VIII型、IX型、X型、XI型、XII型、XIII型、XIV型、XV型、XVI型、XVII型、XVIII型和XIX型胶原蛋白。这些蛋白可呈任何形式,包括但不限于天然和变性形式。在各种实施方案中,一种或多种表面处理可以包括一种或多种碳水化合物,诸如壳多糖、壳聚糖、藻酸和藻酸盐,诸如藻酸钙和藻酸钠。这些材料可从植物产品、人或其它生物体或细胞中分离,或者合成制造。
在各种实施方案中,添加剂可包括天然肽,诸如甘氨酰-精氨酰-甘氨酰-天冬氨酰-丝氨酸(GRGDS)(SEQ ID NO.1)、精氨酰甘氨酰天冬氨酸(RGD)SEQ ID NO.2)和釉原蛋白。在一些实施方案中,表面处理可以包括蔗糖、果糖、纤维素或甘露醇。在一些实施方案中,添加剂可包括营养物,诸如牛血清白蛋白。在一些实施方案中,添加剂可包括维生素,诸如维生素B2、维生素Ad、维生素D、维生素E和维生素K。在一些实施方案中,添加剂可包括核酸,诸如mRNA和DNA。在一些实施方案中,添加剂可包括天然或合成的类固醇和激素,诸如地塞米松、氢化可的松、雌激素及其衍生物。在一些实施方案中,添加剂可包括生长因子,诸如成纤维细胞生长因子(FGF)、转化生长因子β(TGF-β)和表皮生长因子(EGF)。在一些实施方案中,添加剂可包括递送载剂,诸如纳米颗粒、微粒、脂质体、病毒和非病毒转染系统。
在各种实施方案中,添加剂可包括一种或多种治疗剂。治疗剂可以是天然或合成药物,包括但不限于:镇痛药、麻醉剂、抗真菌剂、抗生素、抗炎药、非甾体抗炎药(NSAID)、驱虫药、解毒剂、止吐药、抗组胺药、抗癌药、抗高血压药、抗疟药、抗微生物剂、抗精神病药、解热药、防腐剂、抗关节炎药、抗结核药、止咳药、抗病毒药、心脏活性药物、泻药、化疗药、有色或荧光显像剂、皮质激素(诸如类固醇)、抗抑郁药、镇静剂、诊断辅助剂、利尿剂、酶、祛痰药、激素、催眠药、矿物质、营养补充剂、拟副交感神经药、钾补充剂、辐射敏化剂、放射性同位素、荧光纳米颗粒(诸如纳米金刚石)、镇静药、磺胺类药物、兴奋剂、拟交感神经药、安定药、尿道抗感染药物、血管收缩剂、血管扩张剂、维生素、黄嘌呤衍生物等。治疗剂也可以是其它有机小分子、天然分离的实体或其类似物、有机金属剂、螯合的金属或金属盐、基于肽的药物,,或肽或非肽受体靶向或结合剂。
使用生物工程化的DWJM的方法
本发明还涉及使用生物工程化的DWJM的方法。如本文其它地方所述,生物工程化的DWJM具有几个有利性质,包括但不限于能够形成任何所需形状和尺寸的3D结构、孔隙尺寸和孔隙分布的基本均匀性,以及细胞外基质组分的均匀组成。生物工程化的DWJM因此非常适合于许多应用。
细胞培养
在一方面,本发明包括培养细胞的方法。在各种实施方案中,所述方法涉及生物工程化的DWJM用于支持和扩增一种或多种细胞群体的用途。可在任何合适的环境中(包括在体内和体外条件下)培养细胞。可使用本发明的生物工程化的DWJM培养的细胞可以是任何合适的细胞。合适的细胞的非限制性实例包括多能干细胞、胚胎干细胞、造血干细胞、脂肪来源的干细胞、骨髓来源的干细胞、成纤维细胞、骨细胞、上皮细胞、心肌细胞、内皮细胞、神经细胞等。合适的细胞还可包括癌细胞,包括但不限于:白血病、淋巴瘤、骨髓瘤、乳腺癌、前列腺癌、子宫内膜癌、膀胱癌、脑癌、宫颈癌、肺癌、黑色素瘤、宫颈癌、卵巢癌、结直肠癌、胰腺癌、食道癌、肾癌、甲状腺癌、肝癌、子宫癌、软组织肉瘤、骨癌、胃癌等。在一些实施方案中,本发明的生物工程化的DWJM能维持接种于其中的细胞的可塑性。
细胞可从许多来源中分离出来,所述来源包括,例如,来自活受试者的活检组织和从尸体回收的全器官。分离的细胞可以是通过活检从意欲成为受体的受试者中获得的自体细胞。活检物可使用活检针(一种使得过程快速且简单的快速作用的针)来获得。
可使用本领域技术人员已知的技术来分离细胞。例如,可以机械地分解组织和/或用消化酶和/或螯合剂处理组织,所述消化酶和/或螯合剂削弱相邻细胞之间的连接,使得可以将该组织分散成单个细胞的悬浮液而不会造成明显的细胞破裂。酶促分解可通过将组织切碎并用多种消化酶中的任何一种单独或组合处理切碎的组织来完成。这些酶包括但不限于胰蛋白酶、胰凝乳蛋白酶、胶原蛋白酶、弹性蛋白酶和/或透明质酸酶、DNA酶、链霉蛋白酶和分散酶。机械破碎也可通过多种方法完成,所述方法包括但不限于刮擦组织表面,使用研磨机、搅拌器、筛子、均化器、压敏元件(pressure cell)或超声波仪。
一旦组织被简化成单个细胞的悬浮液,就可将悬浮液分级分离成亚群,从所述亚群中可以获得细胞成分。这也可使用用于细胞分离的标准技术来完成,所述标准技术包括但不限于,特定细胞类型的克隆和选择、不想要的细胞的选择性破坏(阴性选择)、在混合群体中基于差异性的细胞可凝集性的分离、冷冻-解冻程序、混合群体中细胞的差异性贴壁特性、过滤、常规和区带离心、离心淘析(逆流离心)、按单位比重分离、反流分配、电泳和荧光激活细胞分选。
例如,当供体患有诸如癌症或向所需组织转移的其它肿瘤的疾病时,细胞分级分离也是期望的。可对细胞群体进行分选,以将恶性细胞或其它肿瘤细胞与正常非癌性细胞分开。从一种或多种分选技术中分离出的正常非癌性细胞然后可用于组织重建。
可在体外培养分离的细胞,以增加可用于接种到生物工程化的DWJM中的细胞的数量。自体细胞的使用可以减少或防止通常见于同种异体细胞的组织排斥。然而,如果受试者在植入人工器官后出现免疫反应,则可使用免疫抑制剂诸如环孢菌素或FK506治疗受试者,以降低排斥的可能性。在某些实施方案中,可将嵌合细胞或来自转基因动物的细胞接种到生物工程化的DWJM上。
分离的细胞可在用遗传物质包被之前进行转染。有用的遗传物质可以是,例如,能够减少或消除宿主中的免疫反应的基因序列。例如,可抑制细胞表面抗原诸如I类和II类组织相容性抗原的表达。这可使移植的细胞被宿主排斥的机会减少。另外,转染也可用于基因传递。
接种的细胞可以是正常的,或可被遗传工程化以提供额外的或正常的功能。可使用用逆转录病毒载体、聚乙二醇或本领域技术人员已知的其它方法对细胞进行遗传工程化的方法。这些包括使用在细胞中运输和表达核酸分子的表达载体。(参见Goeddel;GeneExpression Technology:Methods in Enzymology 185,Academic Press,San Diego,Calif.(1990)。可通过常规转化或转染技术将载体DNA引入到原核生物或细胞中。转化或转染宿主细胞的合适方法可见于Sambrook等人(Molecular Cloning:A Laboratory Manual,第3版,Cold Spring Harbor Laboratory press(2001))和其它实验室教科书中。
可根据标准方法将细胞接种到生物工程化的DWJM上。例如,已经报道了将细胞接种到用于组织修复的聚合物衬底上(参见,例如,Atala,A.等人,J.Urol.148(2Pt 2):658-62(1992);Atala,A.等人,J.Urol.150(2Pt 2):608-12(1993))。可对培养物中生长的细胞进行胰蛋白酶处理以分离该细胞,并且可将分离的细胞接种在生物工程化的DWJM上。替代地,可将从细胞培养物中获得的细胞作为细胞层从培养板上取出,并且可将该细胞层直接接种到生物工程化的DWJM上,而无需预先分离细胞。
在一个实施方案中,将100万至5000万的范围内的细胞悬浮在培养基中,并施加到生物工程化的DWJM的每平方厘米的表面上。将生物工程化的DWJM在标准培养条件(例如,37℃5%CO2)下孵育一段时间,直至细胞附着。然而,应该理解,接种到生物工程化DWJM上的细胞密度可以变化。例如,较高的细胞密度通过接种的细胞促进较大的组织再生,而较低的密度可通过细胞浸润来自宿主的移植物而允许相对较大的组织再生。取决于生物工程化的DWJM和细胞,还可使用其它接种技术。例如,可通过真空过滤将细胞施加到生物工程化的DWJM上。根据本文的教导,细胞类型的选择和将细胞接种到生物工程化的DWJM上对于本领域普通技术人员来说是常规的。
在一些实施方案中,生物工程化的DWJM适用于培养和扩增造血干细胞(HSC)。HSC驻留于骨髓(BM)造血“生态位”(一种调节HSC自我更新和多能性的特殊微环境)中。生物工程化的DWJM可用作三维培养系统,所述三维培养系统重现了BM造血生态位以扩增和分化造血干细胞和祖细胞(HSPC)。简言之,可用PBS洗涤生物工程化的DWJM,并将其在培养基中孵育过夜。然后,可将富集的CD34+HSPC在培养基中在37℃和5%CO2下接种到生物工程化的DWJM上。生物工程化的DWJM能够促进HSPC静止,同时保持它们的生存力和集落形成能力。细胞粘附至生物工程化的DWJM也增加了c-kit+HSPC(具有增强的自我更新能力的群体)的频率。生物工程化的DWJM能够诱导其周围细胞中CXCR4的表达,从而增强HSPC向基质细胞衍生因子-1(SDF-1)的迁移。生物工程化的DWJM还能够上调巨核细胞分化、细胞移动和归巢以及CD34+细胞中的HSC标记基因。
在一些实施方案中,生物工程化的DWJM也适用于HSC的共培养和分化,诸如与间充质基质细胞(MSC)在一起。简言之,如上那样用PBS洗涤生物工程化的DWJM,并将其在培养基中孵育过夜。然后,在添加富集的CD34+HSC群体之前,可将MSC群体接种到生物工程化的DWJM中并保持两天。在与上述相同的培养条件下,与MSC群体结合的生物工程化的DWJM能够高度刺激HSPC的增殖,并通过抑制CXCR4的表达来减少它们的迁移。
在各种实施方案中,可将生物工程化的DWJM与不同类型的细胞、组织和基质材料组合使用,以形成用于移植或体外药物测试的复杂组织和器官。生物工程化的DWJM可适用于三维打印,以形成复杂的组织和器官。
高通量筛选
在一方面,本发明涵盖用于高通量筛选许多药物和治疗剂的方法。生物工程化的DWJM具有高度的可重现性,并且可对其进行尺寸调整和成形以使其适合于任何合适的高通量测试系统。在一些实施方案中,生物工程化的DWJM可用于支持高通量的基于细胞的测定,以筛选药物或疗法的有效性。
本发明的筛选方法不限于特定类型的化合物。潜在的测试化合物包括化学剂(诸如毒素)、药物、肽、蛋白质(诸如抗体、细胞因子、酶等),以及核酸(包括基因药物和引入的基因,所述基因可编码治疗剂诸如蛋白质、反义剂(即包含与靶细胞类型中表达的靶RNA互补的序列的核酸,诸如RNAi或siRNA))、核酶等。另外地或替代地,本发明的测定可筛选物理剂,诸如辐射(例如电离辐射、紫外光或热);这些可以单独测试,也可以与化学剂和其它剂组合测试。在一个实施方案中,筛选整个化合物文库。化合物文库是用于高通量筛选的储存化合物的大集合。化合物文库中的化合物可以彼此没有关系,或者替代地具有共同的特征。例如,假设的化合物文库可含有已知与特定结合区域结合的所有已知化合物。
本发明的测定也可用于测试递送载剂。这些可具有从常规药物制剂到基因递送载剂的任何形式。例如,所述测定可用于比较由两种或多种不同递送系统(例如,贮库制剂和控释制剂)施用的同一化合物的效果。它们也可用来调查特定的载剂本身是否具有影响。随着基于基因的治疗剂的使用增加,与各种可能的递送系统相关的安全性问题变得越来越重要。因此,本发明的模型可用于研究核酸治疗剂的递送系统诸如裸DNA或RNA、病毒载体(例如,逆转录病毒或腺病毒载体)、脂质体等的性质。因此,测试化合物可以是含有或不含任何相关治疗剂的任何合适类型的递送载剂。递送载剂的非限制性实例包括聚合物泡囊(polymersome)、囊泡、胶束、质粒载体、病毒载体等。
例如,白血病干细胞对化学疗法具有抗性,并且被认为在患者获得初始缓解后会导致白血病复发。然而,在传统系统中培养的白血病细胞(即,在培养基中的悬浮液)失去了它们的干细胞特性。在使用本发明的生物工程化的DWJM时,癌症干细胞诸如白血病干细胞可得到维持,并且可用化学治疗剂和其它抗癌剂加以治疗,以筛选针对其干细胞变体的有效性。简言之,可修剪生物工程化的DWJM以使其适合于多孔板的孔,用PBS洗涤所述生物工程化的DWJM,并将其在培养基中孵育以备用于筛选测定。可将制备的生物工程化的DWJM分配到多孔板的每个孔中,接种急性骨髓性白血病(AML)细胞群体,并在37℃、5%CO2下孵育,以在每个孔中建立AML细胞群体。以这种方式培养的AML细胞显示出增殖减少,而未经历明显的分化,其中ALDH+群体增加。化学疗法治疗可通过用新鲜体积的含有高剂量多柔比星的培养基替换每个孔中的培养基来模拟。与悬浮的AML细胞相比,在生物工程化的DWJM中培养的AML细胞表现出较少的凋亡,这表明生物工程化的DWJM能够保持AML细胞的干细胞特性以抵抗多柔比星治疗。白血病细胞附着在基质上已被证明会导致白血病细胞的代谢变化,所述代谢变化通常与白血病细胞对化学疗法的抗性相关。
因此,生物工程化的DWJM可用于筛选抗癌剂在靶向培养于其中的任何化学抗性癌症干细胞的一个或多个群体中的有效性。抗癌剂可包括化学治疗剂、抗细胞增殖剂、放射增敏剂或其任意组合。例如,可以筛选以下非限制性示例性类别的任何常规化学治疗剂:烷化剂;亚硝基脲;抗代谢物;抗肿瘤抗生素;植物生物碱(plant alkyloid);紫杉烷;激素剂;和混杂的剂。另外,可修改生物工程化的DWJM环境以测试基于免疫的疗法,所述基于免疫的疗法包括但不限于接种癌细胞和T淋巴细胞以测试T细胞对癌症的影响。
烷化剂之所以如此命名,是因为它们能够在细胞中存在的条件下将烷基添加到许多负电性基团中,从而干扰DNA复制,防止癌细胞繁殖。大多数烷化剂是非细胞周期特异性的。在特定方面,它们通过使DNA双螺旋链中的鸟嘌呤碱基交联来制止肿瘤生长。非限制性实例包括白消安、卡铂、苯丁酸氮芥、顺铂、环磷酰胺、达卡巴嗪、异环磷酰胺、二氯甲基二乙胺盐酸盐(mechlorethamine hydrochloride)、美法仑、丙卡巴嗪、噻替哌和尿嘧啶氮芥。
抗代谢物在细胞周期的合成(S)期阻止碱基掺入到DNA中,从而阻止正常的发育和分裂。抗代谢物的非限制性实例包括诸如5-氟尿嘧啶、6-巯基嘌呤、卡培他滨、胞嘧啶阿拉伯糖苷、氟尿苷、氟达拉滨、吉西他滨、甲氨蝶呤和硫鸟嘌呤等的药物。
抗肿瘤抗生素一般通过干扰细胞分裂所需的酶或改变围绕细胞的膜来阻止细胞分裂。这些剂是非细胞周期特异性的。抗肿瘤抗生素的非限制性实例包括更生霉素、柔红霉素、伊达比星、丝裂霉素C和米托蒽醌。
植物生物碱抑制或制止有丝分裂或抑制阻止细胞产生细胞生长所需蛋白质的酶。常用的植物生物碱包括长春碱、长春新碱、长春地辛和长春瑞滨。
紫杉烷影响在细胞功能中很重要的被称为微管的细胞结构。在正常细胞生长中,微管在细胞开始分裂时形成,但一旦细胞停止分裂,微管就会被分解或破坏。紫杉烷阻止微管分解,从而使癌细胞被微管堵塞而无法生长和分裂。非限制性示例性紫杉烷包括紫杉醇和多西他赛。
激素剂和激素样药物用于某些类型的癌症,包括例如白血病、淋巴瘤和多发性骨髓瘤。它们经常与其他类型的化学疗法药物一起使用以增强其有效性。性激素用于改变女性或男性激素的作用或产生,并用于减缓乳腺癌、前列腺癌和子宫内膜癌的生长。抑制这些激素的产生(芳香酶抑制剂)或作用(他莫昔芬)经常可用作治疗的辅助手段。一些其他肿瘤也依赖激素。他莫昔芬是干扰促进乳腺癌细胞生长的雌激素活性的激素剂的非限制性实例。
混杂的剂包括化学治疗剂,诸如博莱霉素、羟基脲、L天冬酰胺酶和丙卡巴嗪,它们也可使用生物工程的DWJM来筛选。
抗细胞增殖剂可进一步被定义为凋亡诱导剂或细胞毒性剂。凋亡诱导剂可以是粒酶、Bcl-2家族成员、细胞色素C、半胱天冬酶或其组合。示例性粒酶包括粒酶A、粒酶B、粒酶C、粒酶D、粒酶E、粒酶F、粒酶G、粒酶H、粒酶I、粒酶J、粒酶K、粒酶L、粒酶M、粒酶N或其组合。在其它方面,Bcl-2家族成员包括例如Bax、Bak、Bcl-Xs、Bad、Bid、Bik、Hrk、Bok或其组合。
在一些实施方案中,半胱天冬酶是半胱天冬酶-1、半胱天冬酶-2、半胱天冬酶-3、半胱天冬酶-4、半胱天冬酶-5、半胱天冬酶-6、半胱天冬酶-7、半胱天冬酶-8、半胱天冬酶-9、半胱天冬酶-10、半胱天冬酶-11、半胱天冬酶-12、半胱天冬酶-13、半胱天冬酶-14或其组合。在其它实施方案中,细胞毒性剂为TNF-α、白树毒素、灵菌红素、核糖体抑制蛋白(RIP)、假单胞菌(Pseudomonas)外毒素、艰难梭菌(Clostridium difficile)毒素B、幽门螺杆菌(Helicobacter pylori)VacA、小肠结肠炎耶尔森氏菌(Yersinia enterocolitica)YopT、紫色杆菌素(Violacein)、二乙烯三胺五乙酸、伊洛福芬(irofulven)、白喉毒素、米托洁林、蓖麻毒素、肉毒杆菌毒素、霍乱毒素、皂草素6或其组合。
适用于筛选的另外的抗癌剂包括小分子、肽、蛋白质和合成化合物、诸如:依维莫司、曲贝替定、白蛋白结合型注射用紫杉醇(abraxane)、TLK 286、AV-299、DN-101、帕唑帕尼、GSK690693、RTA 744、ON 0910.Na、AZD 6244(ARRY-142886)、AMN-107、TKI-258、GSK461364、AZD 1152、恩扎妥林(enzastaurin)、凡德他尼、ARQ-197、MK-0457、MLN8054、PHA-739358、R-763、AT-9263、FLT-3抑制剂、VEGFR抑制剂、EGFR TK抑制剂、极光激酶抑制剂、PIK-1调节剂、Bcl-2抑制剂、HDAC抑制剂、c-MET抑制剂、PARP抑制剂、PD-1抑制剂、Cdk抑制剂、EGFR TK抑制剂、IGFR-TK抑制剂、抗HGF抗体、抗CD47抗体、抗GD2抗体、抗EGF受体抗体、PI3激酶抑制剂、AKT抑制剂、JAK/STAT抑制剂、免疫检查点阻断剂、检查点-1或2抑制剂、黏着斑激酶抑制剂、Map激酶激酶(mek)抑制剂、VEGF陷阱抗体、培美曲塞、埃罗替尼、达沙替尼、尼洛替尼、地卡他尼、帕尼单抗、氨柔比星、奥戈伏单抗、Lep-etu、诺拉曲塞、azd2171、巴他布林、奥法木单抗、扎木单抗、艾特咔林、粉防己碱、卢比替康、替米利芬、奥利默森、替西木单抗、伊匹单抗、棉酚、Bio 111、131-I-TM-601、ALT-110、BIO 140、CC 8490、西仑吉肽、吉马替康、IL13-PE38QQR、INO 1001、IPdR1 KRX-0402、硫蒽酮、LY 317615、纽迪(neuradiab)、维特斯潘(vitespan)、Rta 744、Sdx102、他仑帕奈(talampanel)、阿曲生坦、Xr 311、罗米地辛、ADS-100380、舒尼替尼、5-氟尿嘧啶、伏立诺他、依托泊苷、吉西他滨、多柔比星、脂质体多柔比星、5'-脱氧-5-氟尿嘧啶、长春新碱、替莫唑胺、ZK-304709、塞利西利;PD0325901、AZD-6244、卡培他滨、L-谷氨酸、七水合物、喜树碱、PEG标记的伊立替康、他莫昔芬、枸橼酸托瑞米芬、阿那曲唑、依西美坦、来曲唑、DES(二乙基己烯雌酚)、雌二醇、雌激素、缀合的雌激素、贝伐单抗、IMC-1C11、CHIR-258);3-[5-(甲基磺酰基哌啶甲基)-吲哚基-喹诺酮、伏他拉尼、AG-013736、AVE-0005、pyro-Glu-His-Trp-Ser-Tyr-D-Ser(But)-Leu-Arg-Pro-Azgly-NH2 x(醋酸盐)(其中x=1至2.4)、醋酸戈舍瑞林、醋酸亮丙瑞林、醋酸曲普瑞林、醋酸甲羟孕酮、己酸羟孕酮、醋酸甲地孕酮、雷洛昔芬、比卡鲁胺、氟他胺、尼鲁米特、醋酸甲地孕酮、CP-724714、TAK-165、HKI-272、埃罗替尼、拉帕替尼、卡奈替尼、ABX-EGF抗体、爱必妥、EKB-569、PKI-166、GW-572016、洛那法尼(Ionafarnib)、BMS-214662、替匹法尼(tipifarnib);氨磷汀、NVP-LAQ824、辛二酰苯胺异羟肟酸、丙戊酸、曲古抑菌素A、FK-228、SU11248、索拉非尼、KRN951、氨格鲁米特(aminoglutethimide)、阿那沙林(arnsacrine)、阿那格雷、L-天冬酰胺酶、卡介苗(BCG)疫苗、博莱霉素、布舍瑞林、白消安、卡铂、卡莫司汀、苯丁酸氮芥、顺铂、克拉屈滨、氯膦酸盐、环丙孕酮、阿糖胞苷、达卡巴嗪、更生霉素、柔红霉素、二乙基己烯雌酚、表柔比星、氟达拉滨、氟氢化可的松、氟甲睾酮、氟他胺、吉西他滨、羟基脲、伊达比星、异环磷酰胺、伊马替尼、亮丙瑞林、左旋咪唑、洛莫司汀、二氯甲基二乙胺、美法仑、6-巯基嘌呤、美司那、甲氨蝶呤、丝裂霉素、米托坦、米托蒽醌、尼鲁米特、奥曲肽、奥沙利铂、帕米膦酸盐(pamidronate)、喷司他丁、普卡霉素、卟吩姆钠、丙卡巴肼、雷替曲塞、利妥昔单抗、链脲菌素、替尼泊苷、睾酮、沙立度胺、硫鸟嘌呤、噻替哌、维甲酸、长春地辛、13-顺式视黄酸、苯丙氨酸氮芥、尿嘧啶氮芥、雌莫司汀、六甲蜜胺、氟尿苷、5-脱氧尿苷、胞嘧啶阿糖核苷、6-巯基嘌呤、脱氧助间型霉素、骨化三醇、戊柔比星、光辉霉素、长春碱、长春瑞滨、拓扑替康、雷佐生(razoxin)、马立马司他、COL-3、新伐司他、BMS-275291、角鲨胺、内皮他丁、SU5416、SU6668、EMD121974、白细胞介素-12、IM862、血管他丁、维他辛、屈洛昔芬、吲哚西芬(idoxyfene)、螺内酯、非那雄胺、西咪替丁、曲妥珠单抗、地尼白介素(denileukindiftitox)、吉非替尼、硼替佐米、紫杉醇、不含cremophor的紫杉醇、多西他赛、埃博霉素B、BMS-247550、BMS-310705、屈洛昔芬、4-羟基他莫昔芬、哌喷昔芬、ERA-923、阿佐昔芬、氟维司群、阿考比芬、拉索昔芬、艾多昔芬、TSE-424、HMR-3339、ZK186619、拓泊替康、PTK787/ZK222584,VX-745,PD184352、雷帕霉素、40-O-(2-羟基乙基)-雷帕霉素、坦罗莫司、AP-23573、RAD001、ABT-578、BC-210、LY294002、LY292223、LY292696、LY293684、LY293646、渥曼宁青霉素、ZM336372、L-779、450、PEG-非格司亭、达贝泊汀(darbepoetin)、促红细胞生成素、粒细胞集落刺激因子、唑仑二膦酸盐(zolendronate)、强的松、西妥昔单抗、粒细胞巨噬细胞集落刺激因子、组胺瑞林、聚乙二醇化干扰素α-2a、干扰素α-2a、聚乙二醇化干扰素α-2b、干扰素α-2b、阿扎胞苷、PEG-L-天冬酰胺酶、来那度胺、吉姆单抗、氢化可的松、白介素-11、地拉佐生、阿仑珠单抗、全反式维甲酸、酮康唑、白细胞介素-2、甲地孕酮、免疫球蛋白、氮芥、甲泼尼龙、替伊莫单抗(ibritgumomab tiuxetan)、雄激素、地西他滨、六甲嘧胺、贝沙罗汀、托西莫单抗、三氧化二砷、可的松、羟乙膦酸钠(editronate)、米托坦、环孢霉素、脂质体柔红霉素、埃德温娜(Edwina)-天冬酰胺酶、锶89、卡索匹坦、奈妥替坦、NK-1受体拮抗剂、帕洛诺司琼、阿瑞匹坦、苯海拉明、羟嗪、甲氧氯普胺、劳拉西泮、阿普唑仑、氟哌啶醇、氟哌利多、屈大麻酚、地塞米松、甲泼尼龙、丙氯拉嗪、格拉司琼、昂丹司琼、多拉司琼、托烷司琼、聚乙二醇化非格司亭、促红细胞生成素、依泊汀α、达贝泊汀α及其组合。
还可将生物工程化的DWJM与免疫细胞结合,以筛选许多免疫疗法的有效性。免疫疗法可包括T细胞疫苗接种,其通常涉及用灭活的自体反应性T细胞进行免疫,以消除癌细胞群体。另一种免疫疗法涉及使用双特异性T细胞募召剂(bispecific T-cell Engager)(BiTE),其为被设计成同时与如本文所述的内源T细胞和癌细胞上的特定抗原结合,从而将这两种类型的细胞连接起来的抗体。在某些实施方案中,免疫疗法采用单克隆抗体(MAb)。MAb刺激破坏癌细胞的免疫反应。类似于由B细胞天然产生的抗体,这些MAb“包被”癌细胞表面,从而触发免疫系统对它的破坏。例如,贝伐单抗靶向血管内皮生长因子(VEGF),所述血管内皮生长因子为由肿瘤细胞和肿瘤微环境中其它细胞分泌的促进肿瘤血管发育的蛋白质。当与贝伐单抗结合时,VEGF不能与其细胞受体相互作用,从而阻止导致新血管生长的信号传导。类似地,西妥昔单抗和帕尼单抗靶向表皮生长因子受体(EGFR),曲妥珠单抗靶向人表皮生长因子受体2(HER-2)。与细胞表面生长因子受体结合的MAb阻止被靶向的受体发送它们的正常生长促进信号。它们还可触发细胞凋亡,并激活免疫系统以破坏肿瘤细胞。
可针对对生物工程化的DWJM中培养的癌症干细胞的有效性进行筛选的进一步的治疗剂包括目前使用的各种放射疗法中的任一种。还可对放射疗法针对它们对由生物工程化的DWJM提供的ECM化合物和结构的影响进行筛选。示例性放射疗法包括但不限于:3D适形放射疗法、调强适形放射疗法、近距离放射疗法、立体定向放射外科治疗、调强质子疗法(intensity-modulated proton therapy)等。
组织工程
在一些实施方案中,生物工程化的DWJM可在体内用于促进细胞的募集、浸润和分化。生物工程化的DWJM中细胞的流入和成熟可用于再生组织以治疗缺陷和伤口。可用本发明的方法来促进闭合的伤口包括但不限于擦伤、撕脱伤、吹伤(blowing wound)、烧伤、挫伤、枪伤、切伤、开放性伤口、穿透伤、穿孔伤、穿刺伤、串线伤、刺伤、手术伤、皮下伤或切线伤。在一些实施方案中,生物工程化的DWJM促进外胚层分化以再生皮肤的各种亚结构,包括汗腺、皮脂腺、毛囊等。可使用缝线、粘合剂或覆盖绷带将生物工程化的DWJM固定到伤口区域。该生物工程化的DWJM可被切割成与伤口的尺寸匹配,或者该生物工程化的DWJM可与伤口边缘重叠。在一些情况下,可使生物工程化的DWJM成形成渗透到由深度伤口形成的空腔中。还可将生物工程化的DWJM用于粘膜损伤的愈合,诸如在手术相关的创伤和事故中。
在一些实施方案中,生物工程化的DWJM是以无细胞形式施加的,使得在植入后,生物工程化的DWJM支持来自天然组织的细胞迁移和增殖。可在无细胞生物工程化的DWJM中补加ECM和其它细胞分泌物,以促进愈合。在其它实施方案中,在生物工程化的DWJM中接种一种或多种细胞群体以形成人工组织构建体。人工组织构建体可以是自体的,其中该细胞群体来源于患者自身的组织,或者是同种异体的,其中该细胞群体来源于与患者同种的另一个受试者。人工器官构建体也可以是异种的,其中不同的细胞群体来源于不同于受试者的哺乳动物物种。例如,细胞可来源于诸如人、猴子、狗、猫、小鼠、大鼠、牛、马、猪、山羊和绵羊等的哺乳动物的器官。
在一些实施方案中,生物工程化的DWJM适合于再生骨组织和修复骨缺损。生物工程化的DWJM可用作生长因子递送的支架,以促进内源性细胞归巢。简言之,可将生物工程化的DWJM的尺寸调整为适合骨折或缺损,并可在该生物工程化的DWJM中加载成骨和血管生成生长因子,包括但不限于骨形态发生蛋白(BMP-2)和血管内皮生长因子(VEGF)。在移植适当尺寸的生物工程化的DWJM之前,可用盐水清洗骨缺损部位。该生物工程化的DWJM能够减小或封闭骨缺损,而不会诱导炎症或免疫原性反应。在一些实施方案中,该生物工程化的DWJM能够形成具有典型的骨形态学的新骨,其具有与天然骨相似的明显髓隙(marrow spaces)。
实验性实施例
参照以下实验性实施例进一步详细描述本发明。这些实施例仅仅是为了说明的目的而提供的,除非另有说明,否则这些实施例无意是限制性的。因此,本发明决不应被解释为限于以下实施例,而是应被解释为涵盖由于本文提供的教导而变得明显的任何和所有变化。
无需进一步描述,据信本领域普通技术人员可使用前面的描述和下面的说明性实施例来制备和利用本发明的化合物并实施所要求保护的方法。因此,以下工作实施例具体指出了本发明的示例性实施方案,并且不应被解释为以任何方式限制本公开的其余部分。
实施例1:用于癌症化疗药物的高通量筛选的生物工程化的脱细胞华通氏胶衍生
的细胞外基质
先前的研究建立了用于测试急性骨髓性白血病(AML)的化学抗性的基于基质的3D模型,其中将白血病细胞与接种在合成支架中的原代骨髓间充质基质细胞(MSC)共培养。在该模型中,白血病细胞显示出增加的化学抗性(Aljitawi OS等人,Leuk Lymphoma,2014,55(2):378-91)。细胞外基质(ECM)是下一步关注的焦点,因为ECM通过富集具有干细胞特性的白血病亚群而在化学抗性中起着重要作用。对于ECM组分,利用脱细胞的华通氏胶基质(DWJM)(图1A),所述脱细胞的华通氏胶基质先前已被例举和表征(Aljitawi OS等人,StemCells Dev,2013,22(1):18-26)。华通氏胶是脐带的胶状结缔组织,其主要支持脐带中的血管。它的组分,诸如胶原蛋白、纤连蛋白、透明质酸和硫酸化蛋白聚糖Franc S等人,Placenta,1998,19(1):95-104;Sobolewski K等人,Biol Neonate,1997,71(1):11-21)也存在于骨造血生态位中(Lo Celso C等人,Nature,2009,457(7225):92-6)。
在正常阴道分娩后,立即从同意的足月妊娠的母亲身上采集脐带。将脐带放入由补充有青霉素800U/mL(Sigma-Aldrich,St.Louis,MO)、链霉素9.1mg/mL(Sigma-Aldrich)和两性霉素0.25mg/mL(Sigma-Aldrich)的乳酸林格氏溶液制成的运输溶液中,并立即在4℃冷藏。脱细胞过程在脐带采集后72小时内开始。简言之,将新鲜的人脐带于4℃的运输溶液中从产房运输。通过将基质从周围的膜和血管结构中分离成大的椭圆形块,在层流安全柜中解剖脐带。然后,通过在4℃下于离心机中以5,000rpm交替使用具有约1,257mOsm/L的渗透压的含有氯化钠、甘露醇、氯化镁和氯化钾的高渗盐溶液和含0.005%Triton X-100的ddH2O来对该基质进行两个循环的渗透冲击。经过两个循环的渗透冲击后,使组织经受阴离子去垢剂(月桂基钠)和琥珀酸钠(Sigma L5777),并交替地经受含重组核酸酶(Benzonase)的缓冲(Tris HCl)水,持续16小时。随后,在4℃下于离心机中以5,000rpm用40%乙醇进行有机溶剂提取,持续10分钟。然后利用离子交换珠(IWT-TMD,Sigma;XAD-16Amberlite珠,Sigma;和Dowel Monosphere 550A UPW珠,Supelco)在ddH2O中于室温下在往复式流通玻璃系统中放置30小时来除去所有去垢剂和其它处理残留物。使用含10%的人重组白蛋白(Novozymes)和10%的DMSO(Sigma)溶液的标准RPMI培养基,采用被开发来以-1℃/分钟冷冻至-180℃的材料特异性计算机控制的冷冻曲线对脱细胞的基质进行冷冻保存。
通过冷冻均化,然后冷冻干燥制得了可高重现的DWJM圆盘。将该制造工艺应用于DWJM,以产生具有均匀厚度和孔隙率的基质薄片。这些薄片可被制成不同的尺寸和形状,并可被修剪成任何形状或形式。例如,通过使用穿孔活检试剂盒(punch biopsy kit),可将均匀的圆盘制成适合于96孔板,以创建适合于药物和小分子高通量筛选的平台。在目前应用的方案中,使用0.5g组织/mL蒸馏水来制备用于支架的组织浓度。组织浓度影响DWJM圆盘的孔隙率。
实施方案2:非均化的DWJM与生物工程化的DWJM之间的质谱比较
图6A至图6D和图7A至图7B描绘了示例性75mg/mL的非均化的DWJM切片与尺寸相当的生物工程化的DWJM的切片之间的质谱分析结果。非均化的DWJM的切片可具有丰度比均匀分布的生物工程的DWJM中的丰度少几倍的基质组分。例如,与尺寸相当的非均化的DWJM的切片相比,生物工程化的DWJM可具有介于约30与35之间的纤维蛋白原γ链丰度比、介于10与15之间的肌球蛋白-9丰度比,以及介于约10与15之间的肌球蛋白-10丰度比。这种差异是由于非均化的DWJM的不一致性导致的,因为其组成在其所源自的每根脐带之间以及在其所源自的每根脐带的区域之间是不同的。
实施方案3:DWJM贴壁通过改变白血病细胞代谢来在原发性急性骨髓性白血病中
诱导化疗抗性
先前的研究表明,在脱细胞的华通氏胶(WJ)基质(DWJM)(脐带组织中的凝胶状材料)中培养白血病细胞系会导致化疗抗性。为了减少WJ基质的不同部分之间的生化组成的变化性,并为了优化用于原发性急性骨髓性白血病(AML)细胞的体外培养的基于三维(3D)DWJM的细胞外基质(ECM)模型,通过均化人DWJM,然后冻干人DWJM来制造具有均匀架构和孔隙尺寸的DWJM衍生的多孔圆盘。以下研究检查了DWJM圆盘是否支持原代白血病细胞并导致化疗抗性。
将通过白细胞去除术采集的AML患者样品在DWJM圆盘中培养一周。首先吸出非贴壁细胞,单独地分离出贴壁细胞并评估其生存力、凋亡和集落形成单位(CFU)。培养结束时执行RNA测序。还评估了多柔比星治疗后对化学疗法的反应。对于所有研究,将DWJM贴壁细胞和非贴壁细胞与悬浮培养对照进行比较。使用酶联免疫吸附测定(ELISA)进行代谢途径分析。使用单尾t检验进行组间比较
与以前的研究一致,贴壁的DWJM细胞表现出较少的凋亡(P=0.027)和具有较大且更致密的集落的较高的CFU活性(1/50,000个细胞对比4/50,000个细胞,P=0.0008)。与悬浮培养细胞的处理相比,原代AML样品与DWJM的共培养减少了多柔比星诱导的细胞死亡(P=.047),保持了CFU活性(3.3/300,000个细胞对比0.3/300,000个细胞,P=.047)。为了了解与DWJM的共培养物增强白血病祖细胞功能和治疗抗性的机制,进行了RNA-Seq分析。第7天的RNA-Seq数据分析表明,与悬浮细胞群体相比,贴壁细胞群体中FAM83A和MIR34A显著上调,BPI、ZNF521、NHLH2、CD69、FKBP14、PBX1、TANC1、GRIN2b、MYO6、INHBA、SA1008、CXCL1、A1009、BLNK、MMP9、BHLHE41和CD9显著下调(校正后的P值<0.05)。创新通路分析(IngenuityPathway Analysis)(IPA)将谷氨酸盐受体信号传导鉴定为受影响最大的典型途径,表明主要代谢过程在这两种培养条件之间存在差异。另外,IPA显示FAM83A是上调最多的分子,而MT-TH和MT-TW是贴壁细胞中下调最多的分子中的两种。与悬浮液对照相比,DWJM培养条件与培养上清液中乳酸盐的显著增加(P=0.020)和葡萄糖的显著减少(P=0.005)相关。
因此,本研究证明了DWJM圆盘能支持原代白血病细胞存活。DWJM贴壁细胞显示出与糖酵解的诱导相关的化疗抗性。基于RNA Seq数据,证明了贴壁于DWJM的白血病细胞能上调FAM83A,所述FAM83A在表皮生长因子受体(EGFR)信号通路中起作用。已知FAM83A控制PI3K-AKT-TOR信号传导级联。已知M-TOR进而激活调节糖酵解的HIF-1α途径(图9)。另外,线粒体相关分子(MT-TH和MT-TW)的下调与贴壁细胞中从氧化磷酸化向糖酵解的转变一致。
本文引用的每一个专利、专利申请和出版物的公开内容由此通过引用整体并入本文。虽然已参考特定实施方案公开了本发明,但很明显,在不脱离本发明的真实精神和范围的情况下,本领域的其它技术人员可以设计出本发明的其它实施方案和变型。所附权利要求书旨在被解释为包括所有此类实施方案和等同变化。
序列表
<110> 罗切斯特大学(University of Rochester)
奥马尔·阿利塔韦(Aljitawi, Omar)
哈尼·阿瓦德(Awad, Hani)
迈克尔·贝克尔(Becker, Michael)
<120> 生物工程化的华通氏胶衍生的细胞外基质
<130> 204606-0099-00WO
<150> 62/650,551
<151> 2018-03-30
<160> 2
<170> PatentIn version 3.5
<210> 1
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 化学合成的
<400> 1
Gly Arg Gly Asp Ser
1 5
<210> 2
<211> 3
<212> PRT
<213> 人工序列
<220>
<223> 化学合成的
<400> 2
Arg Gly Asp
1
Claims (28)
1.一种多孔基质,其包含中位孔隙尺寸范围为约200μm至约350μm的模制的脱细胞华通氏胶基质(DWJM)。
2.如权利要求1所述的多孔基质,其中所述中位孔隙尺寸的范围为约230μm至约330μm。
3.如权利要求1所述的多孔基质,其中所述中位孔隙尺寸为约235μm、约275μm、约290μm、约300μm、约310μm、约320μm或约330μm。
4.如权利要求1-3中任一项所述的多孔基质,其中孔隙尺寸分布不超过所述中位孔隙尺寸的50%或17%。
5.如权利要求1-4中任一项所述的多孔基质,具有介于约80%与95%之间的体积孔隙率。
6.如权利要求1-5中任一项所述的多孔基质,还包含均匀分布的选自由以下组成的组的基质组分:胶原蛋白、纤连蛋白、肌腱蛋白C(TN-C)、原纤蛋白、基膜聚糖蛋白、透明质酸(HA)、多功能蛋白聚糖、纤维蛋白原γ链、肌球蛋白-9、肌球蛋白-10、paladin、细丝蛋白、纽蛋白、膜突蛋白、骨膜蛋白、层粘连蛋白、踝蛋白-1以及它们的组合。
7.如权利要求1-6中任一项所述的多孔基质,所述多孔基质的纤维蛋白原γ链丰度比在约30与35之间。
8.如权利要求1-7中任一项所述的多孔基质,所述多孔基质的肌球蛋白-9丰度比在约10与15之间。
9.如权利要求1-8中任一项所述的多孔基质,所述多孔基质的肌球蛋白-10丰度比在约10与15之间。
10.如权利要求1-9中任一项所述的多孔基质,其中所述基质被模制或修剪成尺寸适合于细胞培养孔的圆盘形状。
11.如权利要求1-10中任一项所述的多孔基质,所述多孔基质还包含至少一个接种的细胞的群体。
12.如权利要求1-11中任一项所述的多孔基质,所述多孔基质还包含至少一种治疗剂。
13.一种制备生物工程化的基质的方法,所述方法包括以下步骤:
将脱细胞的华通氏胶基质(DWJM)浸渍在液体介质中;
对浸渍的DWJM执行一个或多个均化循环以形成均化的DWJM,每个均化循环均包括均化期和休止期;
使所述均化的DWJM成形;
将所述均化的DWJM冷冻;以及
将冷冻的所述DWJM在真空下冻干以形成生物工程化的基质。
14.如权利要求13所述的方法,其中所述液体介质是蒸馏水。
15.如权利要求13-14中任一项所述的方法,其中对保存在冰上的浸渍的DWJM执行所述一个或多个均化循环。
16.如权利要求13-15中任一项所述的方法,其中每个均化循环包括约30秒的均化期和约120秒的休止期。
17.如权利要求13-16中任一项所述的方法,其中每个均化周期包括在所述浸渍的DWJM中激活分散混合器。
18.如权利要求13-17中任一项所述的方法,其中执行至少30个均化循环。
19.如权利要求13-18中任一项所述的方法,其中使用3D打印来使所述均化的DWJM成形。
20.如权利要求13-19中任一项所述的方法,其中使用模具使所述均化的DWJM成形。
21.如权利要求13-20中任一项所述的方法,其中在约-80℃与-180℃之间执行冷冻步骤。
22.如权利要求13-21中任一项所述的方法,其中在约-20℃与-60℃之间、在约0.05毫巴下执行冻干步骤。
23.一种促进受试者的骨再生的方法,所述方法包括以下步骤:
提供权利要求1-12中任一项所述的多孔基质;
在所述基质中加载一种或多种成骨和血管生成生长因子;以及
将所述多孔基质植入在所述受试者的骨缺损处。
24.一种培养造血干细胞的方法,所述方法包括将CD34+细胞接种到权利要求1-12中任一项所述的多孔基质上的步骤,其中所述细胞在所述多孔基质上培养时保持在静止期。
25.如权利要求24所述的方法,其中接种的所述CD34+细胞具有巨核细胞谱系偏倚。
26.一种癌症模型,所述癌症模型包括:
权利要求1-12中任一项所述的多孔基质;和
包埋在所述多孔基质中的癌细胞群体。
27.如权利要求26所述的癌症模型,其中所述癌细胞群体表现出癌症干细胞特征。
28.如权利要求26-27中任一项所述的癌症模型,其中所述癌细胞群体选自由以下组成的组:白血病、淋巴瘤、骨髓瘤、乳腺癌、前列腺癌、子宫内膜癌、膀胱癌、脑癌、宫颈癌、肺癌、黑色素瘤、宫颈癌、卵巢癌、结直肠癌、胰腺癌、食道癌、肾癌、甲状腺癌、肝癌、子宫癌、软组织肉瘤、骨癌和胃癌。
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---|---|---|---|---|
CN113662970A (zh) * | 2021-08-30 | 2021-11-19 | 杭州易文赛生物技术有限公司 | 一种脐带干细胞制剂在制备治疗骨关节炎药物中的应用 |
CN113717931A (zh) * | 2021-09-03 | 2021-11-30 | 杭州捷诺飞生物科技股份有限公司 | 一种防收缩人工真皮及其制备方法 |
CN114533959A (zh) * | 2022-04-02 | 2022-05-27 | 山东隽秀生物科技股份有限公司 | 一种肌腱修复材料、制备方法及在制备肌腱修复产品中的应用 |
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102198292A (zh) * | 2010-03-26 | 2011-09-28 | 卢世璧 | 组织工程用脐带去细胞Wharton胶支架及其制备方法 |
CN107158465A (zh) * | 2017-06-29 | 2017-09-15 | 西北民族大学 | 一种骨支架复合材料的制备方法 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110165676A1 (en) | 2009-11-06 | 2011-07-07 | The Children's Mercy Hospital | Method for decellularization |
US9814802B2 (en) | 2012-04-30 | 2017-11-14 | The University Of Kansas | Method for promoting hair growth comprising implanting a tissue scaffold comprising CK-19 positive cells derived from Wharton's jelly mesenchymal stromal cells |
-
2019
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102198292A (zh) * | 2010-03-26 | 2011-09-28 | 卢世璧 | 组织工程用脐带去细胞Wharton胶支架及其制备方法 |
CN107158465A (zh) * | 2017-06-29 | 2017-09-15 | 西北民族大学 | 一种骨支架复合材料的制备方法 |
Non-Patent Citations (4)
Title |
---|
JAE-WON SHIN等: "Extracellular matrix stiffness causes systematic variations in proliferation and chemosensitivity in myeloid leukemias", 《SHIN AND MOONEY》 * |
JAE-WON SHIN等: "Extracellular matrix stiffness causes systematic variations in proliferation and chemosensitivity in myeloid leukemias", 《SHIN AND MOONEY》, vol. 113, no. 43, 10 October 2016 (2016-10-10), pages 12126, XP055607799, DOI: 10.1073/pnas.1611338113 * |
TONGGUANG XIAO ET AL.: "Fabrication and In Vitro Study of Tissue-Engineered Cartilage Scaffold Derived from Wharton’s Jelly Extracellular Matrix", 《BIOMED RESEARCH INTERNATIONAL》, vol. 2017, 29 October 2017 (2017-10-29), pages 1, XP055607407, DOI: 10.1155/2017/5839071 * |
李水军等主编: "《液相色谱-质谱联用技术临床应用》", 上海科学技术出版社, pages: 72 - 73 * |
Cited By (5)
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---|---|---|---|---|
CN113662970A (zh) * | 2021-08-30 | 2021-11-19 | 杭州易文赛生物技术有限公司 | 一种脐带干细胞制剂在制备治疗骨关节炎药物中的应用 |
CN113662970B (zh) * | 2021-08-30 | 2023-11-24 | 杭州易文赛生物技术有限公司 | 一种脐带干细胞制剂在制备治疗骨关节炎药物中的应用 |
CN113717931A (zh) * | 2021-09-03 | 2021-11-30 | 杭州捷诺飞生物科技股份有限公司 | 一种防收缩人工真皮及其制备方法 |
CN114533959A (zh) * | 2022-04-02 | 2022-05-27 | 山东隽秀生物科技股份有限公司 | 一种肌腱修复材料、制备方法及在制备肌腱修复产品中的应用 |
CN114533959B (zh) * | 2022-04-02 | 2022-12-09 | 山东隽秀生物科技股份有限公司 | 一种肌腱修复材料、制备方法及在制备肌腱修复产品中的应用 |
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