关于干细胞治疗
ABOUT STEMCELL
干细胞治疗（自体脂肪来源）是什么？
英迪瓦再生医疗中心遵守厚生劳动省的再生医疗法的规定，并获得了第二类再生医疗等提供计划编号。
什么是干细胞？
我们所有人都有一些细胞，这些细胞具有再生丢失细胞的能力，以维持皮肤和血液等短命细胞的组织不断更新。这些具有这种能力的细胞称为“干细胞”。要被称为干细胞，以下两种能力是必不可少的：一种是产生构成我们身体的各种细胞的能力，如皮肤、红血球和血小板（分化能力），另一种是分裂成具有与自身相同能力的细胞的能力（自我复制能力）。
干细胞大致分为两种类型。一种是干细胞，在特定组织或器官中，如皮肤和血液，继续创造替代细胞。这种类型的干细胞称为“组织干细胞”。组织干细胞不能成为任何东西；它们受到一定的限制，例如造血干细胞只产生血液细胞或神经干细胞只产生神经细胞。另一种是“多能干细胞”，如ES细胞（胚胎干细胞），它可以产生我们体内的任何细胞。换句话说，多能干细胞也可以产生我们体内的各种组织干细胞。诱导多能干细胞（iPS细胞）是从普通细胞人工创造的“多能干细胞”。
利用这些“干细胞”的特性，研究进展迅速，开发出一种新的治疗方法，称为“再生医学”，使用细胞本身作为药物来治疗伤病，并在体外重现体内细胞状态以研究疾病机制。
MSC PRINCIPLE
MSC（间充质干细胞）的原理
MSC移植对糖尿病性心肌病的效果。（a）MSC增强MMP-2的活化并抑制MMP-9的活化，减弱心脏重构。（b）MSC生成VEGF、IGF-1、AM和HGF，刺激受损心肌的肌形成和血管新生。（c）通过分化成心肌细胞和内皮细胞，MSC改善心肌灌注和再生。缩写：AM，肾上腺髓质素；HGF，肝细胞生长因子；IGF-1，胰岛素样生长因子-1；MMP，基质金属蛋白酶；MSC，间充质干细胞；VEGF，血管内皮生长因子。
MSC治疗对糖尿病性多发性神经病的效果。肌肉注射四周后，MSC通过生成bFGF和VEGF沉积在肌纤维间隙中，诱导血管新生并支持神经再生，导致糖尿病性多发性神经病的改善。缩写：bFGF，碱性成纤维细胞生长因子；MSC，间充质干细胞；VEGF，血管内皮生长因子。
间充质干细胞的全身给药可以诱导包括细胞介导作用在内的末端（内分泌）或局部（旁分泌）效应。1) 血管内皮生长因子（VEGF）、胰岛素样生长因子1（IGF-1）、单核细胞趋化蛋白1（MCP1）、碱性成纤维细胞生长因子（bFGF）、白细胞介素6（IL6）2) 干细胞增殖和分化：干细胞因子（SCF）、白血病抑制因子（LIF）、巨噬细胞集落刺激因子（M-CSF）、基质细胞衍生因子1（SDF1）、血管生成素1、活化素A 3) 纤维化抑制：肝细胞生长因子（HGF）、bFGF、肾上腺髓质素（ADM） 4) 抑制细胞凋亡：VEGF、HGF、IGF1、转化生长因子（TGF）β、bFGF、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、活化素A、血小板第1因子。免疫介导作用包括以下内容（5-8） 5) T细胞和B细胞的抑制：人类白细胞抗原G5（HLA G5）、HGF、诱导型一氧化氮合酶（iNOS）、吲哚胺2,3-双加氧酶（IDO）、前列腺素E2（PGE 2）、bFGF、TGFβ 6) 通过TGFβ表达诱导调节性T细胞（Treg）的分化和增殖。 7) 通过分泌IDO、PGE 2和TGFβ抑制自然杀伤（NK）细胞。 8) 通过分泌PGE 2抑制树突状细胞（DC）成熟。
图“Stem Cell Res Ther”由Carrión和Figueroa再现。2011年5月11日；2（3）：23。
注：红色箭头：刺激，黑色箭头：抑制，无钩箭头：直接抑制
缩写：iDC，未成熟树突状细胞；IL，白细胞介素；HGF，肝细胞生长因子；TGF-β，转化生长因子-β；PGE-2，前列腺素E2；IDO，吲哚胺2,3-双加氧酶；NO，一氧化氮；PD-L1，程序性死亡配体1；hMSC，人类间充质干细胞；Treg，调节性T细胞；Th，辅助性T细胞；CTL，细胞毒性T细胞；mDC，成熟树突状细胞；PD-1，程序性细胞死亡蛋白1；PMN，多形核白细胞；NK，自然杀伤细胞
显示动物心脏前脑区局部摄取的融合SPECT/CT图像的矢状面（左）和冠状面（右）的图示，第1天（a）、第2天（b）和第7天（c）。在最后的成像时间点（第5-8天）上，MSC摄取的前顶区（箭头）显示在代表性动物的冠状重建图上。无论最初的局部热点观察如何，前顶分布都存在（仅黄色箭头）。
单离骨髓间质细胞的特征。细胞在密度分级后从骨髓中培养，并显示在接种后48小时（A）和接种后10天（B）。（C）流式细胞术显示这些培养细胞的富集。使用SH2和SH3表面标记的抗体在培养的第2天、第5天和第14天获得的结果。第14天，细胞95-99%均质，对造血细胞常见抗原CD14、CD34（Becton-Dickinson）或CD45（Pharmingen）呈阴性。（D）流式细胞术证明了分离过程的均质性和可重复性。
DISEASE
疾病别治疗法
疾病别老年疾病
多能干细胞具有显著的自我再生能力，并且可以分化为多种不同的细胞类型。越来越多的证据表明，衰老过程可能会对干细胞产生负面影响。随着干细胞的老化，其再生能力下降，并且其分化成各种细胞类型的能力发生变化。因此，干细胞功能因衰老而下降在各种老年相关疾病的病理生理学中起重要作用。了解衰老过程在干细胞功能中的作用，不仅对理解老年相关疾病的病理生理学很重要，而且对开发有效的干细胞疗法治疗未来的老年相关疾病也至关重要。这篇综述文章重点介绍了与各种老年相关疾病相关的干细胞功能障碍的基础。接下来，讨论了一些可能导致老年相关干细胞功能障碍的机制概念。此外，还简要讨论了目前正在开发的用于老年相关干细胞缺陷的潜在疗法。
Citation// World J Exp Med. 2017 Feb 20; 7(1): 1–10.Effect of aging on stem cells. Abu Shufian Ishtiaq Ahmed,et al
疾病别肝脏/糖尿病
再生医学正在转向临床计划，使用干细胞/前体细胞疗法修复受损器官。简要描述位于胆道干的胆道干细胞（hBTSC），它们是肝脏和胰腺共享内胚层干细胞群的器官。它们是肝干/前体细胞在Herings管内的前体，胰腺管腺体的前体。它们在胆管壁内沿径向轴产生成熟系谱，并在十二指肠起点、肝脏或胰腺中的成熟细胞结束的近端-远端轴。多年来，评估移植到肝动脉中的干细胞（胎肝来源的肝干/前体细胞）对各种肝病患者的影响的临床试验一直在进行。不需要免疫抑制。所有对照受试者在给定标准下在一年内死亡或肝功能下降。移植100-150百万个肝干/前体细胞的受试者表现出肝功能和数年存活期的改善。移植的安全性和有效性的评估仍在发展中。用于糖尿病的干细胞疗法使用hBTSC仍在研究中，但可能在正在进行的临床前试验之后进行。此外，间充质干细胞（MSC）和造血干细胞（HSC）正在用于慢性肝病或糖尿病患者。MSC通过旁分泌分泌营养因子和免疫调节因子显示效果，对成熟实质细胞或胰岛细胞的系谱限制有限。HSC的效果主要是通过免疫机制的调节。
Stem Cells. 2013 Oct;31(10):2047-60. doi: 10.1002/stem.1457. Concise review: clinical programs of stem cell therapies for liver and pancreas.Lanzoni G1, Oikawa T
糖尿病
QinanWu, Bing Chen, and Ziwen Liang,
Mesenchymal Stem Cells as a Prospective Therapy for the Diabetic Foot
Stem Cells International Volume 2016, Article ID 4612167, 18 pages
http://dx.doi.org/10.1155/2016/4612167
Figure 1: Mechanisms of the effect of MSC transplantation on diabetic PAD. Mechanisms of recovery effects mediated by stem cell transplantation from two pathways: one is the secretion of angiogenic factors and cytokines, and the other is the transplantation and differentiation into tissue components. Stem cells can specifically enhance local secretion and expression of angiogenic factors and cytokines, contributing to the reconstruction of the microcirculatory system, improvement of blood flow and islet β-cell function, leading to improvement of diabetic PAD. Stem cells can also differentiate into endothelial cells to achieve recovery of endothelial cell dysfunction. These effects may be related to miRNA and MEX.
Figure 2: Mechanisms of the effect of MSC transplantation on diabetic wounds. Recovery of diabetic wounds through MSC transplantation via three pathways: the first is angiogenesis and secretion of factors and cytokines, the second is regulation of the immune system, and the third is transplantation and differentiation into tissue components. Stem cells can specifically enhance local secretion and expression of angiogenic factors and cytokines, contributing to the improvement of diabetic PAD and diabetes. Stem cells can also regulate the activity of T cells, natural killer cells, macrophages, and dendritic cells, inhibiting infection and inflammatory responses. Additionally, MSCs can differentiate into target tissues to achieve repair. These effects may be related to miRNA and MEX.
Figure 3: Mechanisms of the effect of MSC transplantation on diabetic neuropathy. Mechanisms of recovery effects mediated by stem cell transplantation from two pathways: one is the secretion of angiogenic factors, cytokines, and neurotrophic factors, and the other is the transplantation and differentiation into tissue components. Stem cells can specifically enhance local secretion and expression of angiogenic factors and cytokines, contributing to the improvement of diabetic PAD and diabetes itself, leading to the improvement of diabetic neuropathy. Neurotrophic factors can also improve the dysfunction of nerve fibers and nerve conduction. Additionally, stem cells can differentiate into target tissues to achieve repair.
Renal failure
Alfonso Eirin and Lilach O Lerman* Mesenchymal stem cell treatment for chronic renal failure,
Stem Cell Research & Therapy 2014, 5:83 http://stemcellres.com/content/5/4/83
Animals treated with mesenchymal stem cells showed reduced stenosis – renal microvascular loss and fibrosis. Top: Representative micro-CT 3D images showing improved microvascular structure in renal segments of pigs with atherosclerotic renal artery stenosis treated with percutaneous transluminal renal angioplasty (PTRA) and intrarenal MSC injection four weeks earlier. Bottom: Representative renal trichrome staining (×40, blue) showing reduced fibrosis in ARAS + PTRA + MSC-treated pigs.
Clinical applications of MSC: Diabetes
Stem cell transplantation may be a safe and effective treatment for patients with DM. In this series of trials, the best therapeutic results for T1DM were achieved with D34 + HSC therapy, while the worst results for T1DM were observed with HUCB. Diabetic ketoacidosis hindered the therapeutic effect.
A line chart showing changes in C-peptide and HbA1c levels at baseline, 3 months, 6 months, and 12 months after stem cell therapy in patients with T1DM. All data are presented as mean ± SEM. **** P <0.0001 The outcome for stem cell therapy for T2DM Stem cell therapy for type 2 DM.
A-D) Bar charts showing changes in C-peptide and HbA1c levels at baseline and 12 months after administration of different types of stem cells. UC-MSC and PD-MSC were administered intravenously (n = 22 and n = 10, respectively), while UCB and BM-MNC were injected into the pancreas (n = 3 and n = 107, respectively). (E-F) Line charts showing changes in C-peptide and HbA1c levels at baseline, 3 months, 6 months, and 12 months after stem cell therapy for T2D.
Citation// PLoS One. 2016 Apr 13;11(4):e0151938. Clinical Efficacy of Stem Cell Therapy for Diabetes Mellitus: A Meta-Analysis. El-Badawy A, El-Badri N.
疾病别毛囊
Nat Commun. 2012 Apr 17;3:784. doi: 10.1038/ncomms1784.
通过重新排列干细胞及其栖息地实现完全功能性毛囊再生。
Toyoshima KE1, Asakawa K, Ishibashi N, Toki H, Ogawa M, Hasegawa T, Irié T, Tachikawa T, Sato A, Takeda A, Tsuji T.
概要
器官置换再生医学被认为在可预见的未来能够替换因疾病、伤害或衰老损伤的器官。这里我们通过生物工程化的胚芽和孢子胚芽的皮内移植展示了完全功能性的器官再生。这些胚层和胚芽分别由胚胎皮肤来源的细胞和成人干细胞栖息地来源的细胞重构。生物工程化的毛囊发展出正确的结构，并与表皮、后肢肌肉和神经纤维等周围宿主组织形成适当的连接。生物工程化的毛囊还通过毛囊干细胞及其栖息地的重新组织表现出恢复的毛周期和毛头形成。因此，这项研究揭示了使用成人组织来源的毛囊干细胞进行生物工程器官置换疗法的潜力。
(a) Schematic diagram of methods used for the creation and transplantation of bioengineered hair follicle germs. (b) Phase-contrast images of the dorsal skin of mouse embryos, tissue, dissociated single cells, and bioengineered hair follicle germs reconstructed using the organ germ method with nylon thread (arrowhead). Scale, 200 μm. (c) Histological analysis of vibrissae isolated from adult mice. Macroscopic and H&E-stained vibrissae are shown in the left two panels. Dashed lines (red) in macroscopic observation (left) and H&E staining (right) indicate the interface of the bulge and SB region. Boxed area of the left panel is shown at higher magnification in H&E staining to show the bulge and SB region of the right panel. The bulge region is immunostained with anti-CD49f (red, left) and anti-CD34 (red, middle) antibodies and Hoechst 33258 dye (blue). Black dashed lines in high-magnification H&E indicate the interface of the epithelium of the hair follicle. IF, infundibulum; RW, ring body; half of the hair follicle. Scale, 100 μm. (d) Histological and ALP analysis of the bulb region of the vibrissae and initial culture of DP cells. Bulbs (left 2) and cultured DP cells (right 2) were analyzed by ALP enzymatic staining. Red dotted lines indicate Auber’s line. Scale, 100 μm. (e) Longitudinal section of bioengineered hair during the erupting and growth process mediated by the epithelial-mesenchymal plastic device (guided). The corresponding is shown as cyst formation with bioengineered hair follicles at 14 days after intradermal transplantation (unguided). H&E staining (upper) and fluorescence microscopy (lower) of bioengineered hair follicles at 0, 3, and 14 days post-transplantation. Scale, 100 μm. (f) Macroscopic observation of bioengineered hair during the erupting and growth process including post-transplantation day 0 (left), wound healing on day 3, eruption of hair shafts on days 14 and 37 (right), and growth of bioengineered hair in the chest (upper) and spleen (lower). Scale, 1.0 mm.
(a) Histological and immunohistochemical analysis of bioengineered hair (upper) and vibrissae (middle) hair follicles. Boxed areas in low-magnification H&E panels are shown at higher magnification in right panels. Arrows indicate sebaceous glands. Scale, 100 μm. Hair bulbs of bioengineered hair follicles were immunostained with anti-versican (lower left) and α-SMA (arrowhead, lower right) antibodies and enzymatically stained for ALP (lower middle). Scale, 50 μm. (b) Bioengineered human hair produced by transplantation of bioengineered hair follicle germs reconstituted with epithelial cells derived from the bulge and intact DP of human scalp hair follicles. Bioengineered human hair was observed at 21 days post-transplantation (microscopic observation) and analyzed by H&E staining. Species identification of bioengineered hair follicles was analyzed based on nuclear morphological features (right panel). Boxed areas in the inset are shown at higher magnification. Scale, microscope 500 μm, H&E 100 μm, nuclear staining 20 μm. (c) High-density intradermal transplantation of bioengineered hair follicle germs. A total of 28 independent bioengineered hair follicle germs were transplanted into the cervical skin of mice, showing high-density hair growth at 21 days post-transplantation. Scale, 5 mm.
Bioengineered hair and vibrissae were connected with other tissues such as nerve fibers, traction muscles, and striated muscles derived from host or donor cells. Bioengineered hair was connected to smooth muscles as a result of regeneration of the NPNT-expressing bulge region, similar to natural bulge. Neither NPNT expression nor smooth muscle connection was detected in the bioengineered hair bulge region.
Citation/ Fully functional hair follicle regeneration through the rearrangement of stem cells and their niches. Koh-ei Toyoshima, Kyosuke Asakawa, Naoko Ishibashi, Hiroshi Toki, Miho Ogawa, Tomoko Hasegawa, Tarou Irié, Tetsuhiko Tachikawa, Akio Sato, Akira Takeda & Takashi Tsuji. Nature Communications 3, Article number: 784 (2012) doi:10.1038/ncomms1784
疾病别パーキンソン
PD研究および治療で現在利用可能な幹細胞の誘導、分化および適用の概略図。上記の幹細胞は、ESC、NSC、MSC、およびiPSCの4つのカテゴリーに分けることができ、徐々に減少する分化全能性を伴う。 (1) 主に胚盤胞内部塊に由来するESCは、通常の状況下で同時に内胚葉、中胚葉および外胚葉に分化することができる。 場合によっては、ESCもNSCおよびMSCに分化するように誘導することができる。 (2) 特定の脳のニッチから直接単離した、または線維芽細胞から再プログラムしたNSCは、ニューロンおよびほぼすべての神経膠細胞への神経系統の分化を行うことができる。(3) MSCは、主に間葉組織に由来し、中胚葉起源のほとんどすべての細胞に分化することができる。顕著なことに、MSCは誘導プロトコルの特定の組み合わせの下でもDAニューロンに分化するように誘導することができる。(4) OSKM（Oct3 / 4、Sox2、Klf4、およびc-Myc）を導入することにより、成人のヒト体細胞（線維芽細胞など）から再分化させることができるiPSCsは、多系譜分化能を有する有望な幹細胞源である。GMP標準に基づいて、上記の幹細胞および最終分化細胞を、疾患モデル、薬物スクリーニング、およびCRTの実施に適用するために、さらに選別し、精製し、そして拡大することができる。例えば、ESC、MSC、NSC、およびDAニューロンは、以下で使用される。（i）PDモデルの準備（ii）潜在的な薬物スクリーニング;（iii）PDのCRT治療Front. Aging Neurosci., 31 May 2016. A Compendium of Preparation and Application of Stem Cells in Parkinson’s Disease: Current Status and Future Prospects. Yan Shen, Jinsha Huang
RISK
关于干细胞治疗的风险
背景:
间充质基质细胞（MSC"成人干细胞"）在各种临床环境中广泛用于实验。虽然对这些细胞在严重疾病中的使用有兴趣，但这些细胞的安全性尚不清楚。我们进行了系统回顾临床试验，检查使用MSC评估其安全性。
方法和结果：
我们搜索了MEDLINE、EMBASE和CENTRAL（截至2011年6月）。在成人或成人和儿童混合组中使用MSC的血管内给药（静脉或动脉内）进行的临床试验。排除使用分化MSC或其他细胞类型的研究。主要结果根据立即事件（急性输液毒性、发热）、器官系统并发症、感染和长期不良事件（死亡、恶性肿瘤）分类。共审查了2347篇文献，36项研究符合纳入标准。1012名参与者中包括接受治疗的缺血性中风、克罗恩病、心肌病、心肌梗死、移植物抗宿主病和健康志愿者的患者。八项研究是随机对照试验（RCT），有321名参与者。
引用// PLoS One。2012；7（10）：e47559。doi：10.1371/journal.pone.0047559。在线发布2012年10月25日。
间充质基质细胞（SafeCell）细胞治疗的安全性：临床试验的系统评价和荟萃分析。 Lalu MM, McIntyre L, Pugliese C, Fergusson D, Winston BW, Marshall JC, Granton J, Stewart DJ; Canadian Critical Care Trials Group。
REARCH PAPERS
治疗效果的研究论文
Clinical trial with control: stem cell therapy outcome related variables.
| Ref | Diagnosis Number of Cases – Age (Duration of T2DM) | Follow up | Other T2DM Related Therapy | Other T2DM Related Therapy | Other T2DM Related Therapy |
|---|---|---|---|---|---|
| 20 | T2DM1 56 (T), 62 (C) 18-60 y (T=8.6 ± 6.5, C=7.3 ± 6.3) | 1-2-3 mo, every 3 mo until -36 mo | T: Auto BM-MNC Dose ? DPA, 1x C: ( – ) | T: D, E, PST, BGM-MA C: D, E, PST, IIT, BGM-MA | HbA1c and C peptide in treatment were significantly better than either pre-therapy values or control. In Treatment: 18/56 patients insulin was discontinued; 19/56 insulin reduction > 50%, 10/56 insulin reduction 15-50%, 9/56 –non responder In control: 40/62 patients – insulin requirement increased > 50%, 22/62 patients – increased 15-45%. |
| 21 | T2DM 20 (MNC-HBO), 20 (MNC), 20 (C1=HBO), 20 (C2) 40-65 y (2 – 15 y) | 3-6-9-12 mo | Auto BM-MNC T1: MNC-HBO= 3641.2 ± 1585.4 M T2: MNC= 4012.5 ± 1431.9M DPA – 10 minutes 1x | T and C: D, L, PST, SBGM- IA | Insulin dose reduction at 12 mo in T1 and T2, C1, C2 – unchanged Insulin free: T1: 1/20, T2: 2/20 Improvement at 12 mo in AUC C-Pep of T1= T2 > C1, and AUC Ins of T1 and T2. HbA1c at 3, 6, 9 and 12 mo -reduced significantly both in T1 and T2, but stable in C1 and C2. FBG at 6, 9 and 12 months – T1 and T2 -reduced Fasting C peptide at 3, 6, 9 and 12 mo significantly elevated in T1 and T2, but remained stable in C1 and C2 |
| 22 | T2DM 11 (T), 10 (C) T=46.5–56 y (10-15.5 y) C= 52.5–56 y (16-21 y) | 2-4-6-8-10- 12wk-4-5-6- 9-12 mo | T: auto BM- MNC – 290 M (220 -380 M) C: sham, saline SP/DA -1x after 12 wk: PB- GCSF- leucopheresis MNC – 490 (290–730M) C: sham, saline –IV-1x | T and C: D, L, E, W-SBGM – IA | 12 mo: 50% Insulin reduction -Tr: 9/11 = 82%, -C:0/10, p= 0.002 Insulin red Tr > C (p=0.001, 6 mo), (p=0.004, 12 mo) HbA1C maintenance (<7%): Tr 10/11 (91%), C 6/10 (60%), p= 0.167 Increase in glucagon stimulated C peptide: Tr > C, p= 0.036 Correlation insulin decrease-C peptide increase r= 0.8, p=0.01 |
| 23 | T2DM 10 (MSC), 10 (MNC), 10 (C) MSC= 36-58 (8-23) MNC= 39.5-50 (8.5-15) C= 43-59 (9-15) | 2-4-8-12- wk-6-9-12 mo | AutoBM-MSC-P4-5 – 1M/ kg BW Auto BM-MNC – 1B/patient C= vit. B complex SPDA – 1x | T and C: L, PST,D-SBGM- IA | 6/10 (MSC), 6/10 (MNC), 0/10 (C) achieved primary end point: 50% insulin requirement reduction, while maintaining HbA1c <7.0% -> significant difference MNC group: Increase in glucagon stimulated C peptide MSC group: Improvement in insulin sensitivity index and increase in IRS-1 gene expression |
| 24 | T2DM 31 (T), 30(C) 18-60 y (T=8.93±5.67 C=8.3±6.07) | 36 mo | T: Wharton jelly MSC P4 1M/kg BW C: Saline IV – 2x (interval 4 wk) | T and C: D, E, PST, SBGM- MA | Blood glucose, HbA1c, Cpeptide, homeostasis model assessment of pancreatic islet cell function signifi- cantly improved- compared to control. Incidence of diabetic complications: Tr – no increase vs baseline, C: 4/30- new diabetic retinopathy, 3/30 new diabetic neuropathy 3/30 new diabetic nephropathy –> statistically significant difference (Tr vs C, P= 0.007) Insulin dose reduction: Tr: 18/31- 50% insulin dose reduction ( where 10/31 – insulin free from 311 mo postWJMSC, and insulin free duration 12.5±6.8 months),5/31 -1550% reduction, and 8/31 non responder Control: 14/30: >50% insulin dose increase, 16/30: 1545% insulin dose increase – 30/30 – non responder |
| 25 | T2DM + impotence2 7 (T), 3 (C) 57-87 (12-52 y, impo- tence minimal 6 months) | 2wk – 11 mo | T: UCB SC -His tos- tem, ABO, HLA- ABC, DR, and sex- matched – 15M C: saline Injection – CC -1x | T and C:PST, D-SBGM-MA | Tr: Blood glucose levels decreased by 2 weeks, and medication dosages were reduced for 4 to 7 months (6/7). HbA1c levels improved after treatment for up to 3 to 4 months (7/7) Reduced insulin dose after 1 month (2/7) Control: no improvement in blood glucose level, HbA1c, and insulin dose. |
| 26 | T2DM3 15 (T1), 15 (T2), 15 (T3), 3×5 C) T1= 57.7±8.2y (10.8± 7.3y ) T2= 55.3±11.4y (10.2± 5.7y) T3= 57.2 ±6.6y (9.6±4.5y) C= 58.7 ±7.3y (9.8±6.7y) | 12 wk 2y post study | MPC- P(?) Rexleme- strocel-L – mesoblas Inc, cryo-thawed T1=0.3 M/kg T2=1 M/kg T3=2 M/kg C= placebo IV- 45 minutes 1X | T and C: L, PST, BGM-RT | Tr: HbA1c – reduced – at all time points after week 1, C: a small increase in HbA1c Clinical target HbA1c <7% was achieved by 0/15 of Control, 2/15 of T1, 1/15 of T2, and 5/15 of T3 (P < 0.05) Glycemic rescue therapy was required by: 1/15 of Con- trol, 2/15 of T1, 0/15 of T2, 1/15 of T3 |
| 27 | T2DM4 13 (T), 13 (C) 10-58 y (0.5 – 11 y) | 1y | Hu fetal liver HSC – 35-55 M (20% CD34)- cryo-thawed Saline (C) IV – 1x | T and C: BGM-FU | Up to 1 y, no significant improvement in fasting blood glucose, and C peptide compared to control. Improvement in – HbA1c only at 6th mo: 7.9±1.3 in treatment vs 7.0 ± 0.86 in control (p=0.046). None of the treatment become insulin free |
Ref= reference number, T2DM= Type 2 diabetes mellitus, treatment control allocation: 1 patient option, 2 successive: 2 Treatment – 1 Control, others: random, 3single blind multi center (18 –USA), 4=T2DM and T1DM, T= treatment, C= control, y= year(s), MNC= mononuclear cell, HBO= hyperbaric oxygen, MSC= mesenchymal stem cell, mo= month(s), wk= week(s)
SC= stem cell, Auto= autologous, BM= bone marrow, ?= data not available, DPA= dorsal pancreatic artery/substitute, M= million, SP/DA= superior pancreatic or duodenal artery, PB= peripheral blood, GCSF= granulocyte colony stimulating factor, IV- intra venous, P= passage, BW= body weight, B= billion, vit.= vitamin, SPDA= superior pancreaticoduode- nal artery, UCB= umbilical cord blood, CC= corpora cavernosa (penile root clamped with a band 30 min), MPC= mesenchymal progenitor cell, cryo= cryopreserved, hu= human, HSC= haematopoeitic stem cell, cryo= cryopreserved,D= diet, E= exercise, PST= previous standard therapy, BGM = blood glucose monitoring, MA= medication adjustment, IIT= insulin intensification therapy, L= lifestyle, SGBM= self blood glucose monitoring, IA= insulin adjustment, W-SGBM= weekly SGBM, D-SGBM= daily SGBM (minimum 5 points/week), RT= rescue therapy using oral anti diabetic agent, except thiazolidinediones in case there was unacceptable hyperglycemia, FU= at follow up
Current Stem Cell Research & Therapy, 2018(13)
Towards Standardized Stem Cell Therapy in Type 2 Diabetes Mellitus: A Systematic Review
Jeanne Adiwinata Pawitan, Zheng Yang, Ying Nan Wu and Eng Hin Lee
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