Department of Surgery, Cooper University Hospital, Camden, New Jersey, USA.
Cooper Research Institute, Cooper University Hospital, Camden, New Jersey, USA.
Cell Biochem Funct. 2021 Apr;39(3):432-441. doi: 10.1002/cbf.3609. Epub 2020 Dec 21.
Stem cell therapy promotes tissue regeneration and wound healing. Efforts have been made to prime stem cells to enhance their regenerative abilities. Certain marijuana components, namely the non-psychoactive cannabidiol (CBD) and psychoactive tetrahydrocannabinol (THC), are defined as immunomodulators. We test whether two sources of stem cells, primed with CBD or THC, would demonstrate improved regenerative abilities. Human adipose-derived stem cells (ASCs) and bone marrow-derived stem cells (BMDSCs), not obtained from the same individual, were treated with low (300 nM) or high (3 μM) concentration CBD. Porcine ASCs and BMDSCs were isolated from a single pig, and treated with either low or high concentrations of CBD or THC. Transwell migration and MTT proliferation assays were performed on the human ASCs and BMDSCs. Also, transwell migration assay was performed on the porcine ASCs and BMDSCs. Finally, a wound healing scratch assay in porcine primary fibroblasts (PFs) was performed, co-cultured with the cannabinoid-treated ASCs. CBD priming at low concentration induces migration by 180% (P < .01) in porcine ASCs, and by only 93% (P < .02) in porcine BMDSCs. In porcine stem cells, THC priming at low concentration induces migration by 91.6% (P < .01) in ASCs but by only 44.3% (P < .03) in BMDSCs. Compared to PFs co-cultured with untreated ASCs, PFs co-cultured with low CBD-primed ASCs had 75% faster wound closure at 18 hours (P < .01). CBD and THC priming of ASCs and BMDSCs, particularly at lower doses, enhances a number of regenerative parameters, suggesting that these major marijuana components may improve stem cell-based therapies. SIGNIFICANCE OF THE STUDY: Our study demonstrates that cannabinoids can enhance the regenerative capacity of two major sources of stem cells, adipose- and bone marrow-derived, from human and porcine donors. Stem cell isolation and expansion is invasive, costly and time consuming. Stem cells with improved regenerative properties may be effective in the treatment of acute or chronic wounds. This is the first study to compare the priming potential of two sources of stem cells from the same animal, with the same genetic and epigenetic profile, as well as the first to prime with THC.
干细胞疗法可促进组织再生和伤口愈合。人们已经努力使干细胞成熟，以增强其再生能力。某些大麻成分，即非精神活性大麻二酚 (CBD) 和精神活性四氢大麻酚 (THC)，被定义为免疫调节剂。我们测试了两种来源的干细胞，用 CBD 或 THC 进行预处理，是否会显示出更好的再生能力。人类脂肪来源的干细胞 (ASCs) 和骨髓来源的干细胞 (BMDSCs) 并非来自同一供体，用低 (300nM) 或高 (3μM) 浓度的 CBD 处理。从同一头猪中分离出猪 ASC 和 BMDSC，并用低或高浓度的 CBD 或 THC 处理。对人 ASC 和 BMDSC 进行 Transwell 迁移和 MTT 增殖检测。此外，还对猪 ASC 和 BMDSC 进行 Transwell 迁移检测。最后，在猪原代成纤维细胞 (PFs) 中进行了划痕愈合实验，与经大麻素处理的 ASC 共培养。低浓度 CBD 预处理可使猪 ASC 迁移增加 180%（P<0.01），而仅使猪 BMDSC 迁移增加 93%（P<0.02）。在猪干细胞中，低浓度 THC 预处理可使 ASC 迁移增加 91.6%（P<0.01），但仅使 BMDSC 迁移增加 44.3%（P<0.03）。与与未处理的 ASC 共培养的 PFs 相比，与低浓度 CBD 预处理的 ASC 共培养的 PFs 在 18 小时时伤口闭合速度快 75%（P<0.01）。CBD 和 THC 对 ASC 和 BMDSC 的预处理，特别是在较低剂量下，增强了许多再生参数，表明这些大麻的主要成分可能改善基于干细胞的治疗方法。研究的意义：我们的研究表明，大麻素可以增强两种主要来源的干细胞的再生能力，这些干细胞来自人类和猪供体的脂肪和骨髓。干细胞的分离和扩增是侵入性的、昂贵的且耗时的。具有改善的再生特性的干细胞可能有效治疗急性或慢性伤口。这是第一项比较同一动物的两种来源的干细胞的成熟潜力的研究，这些干细胞具有相同的遗传和表观遗传特征，也是第一项用 THC 进行预处理的研究。
