bims-engexo 2024-08-04 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2024–08–04
six papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Exosomes: the next-generation therapeutic platform for ischemic stroke.
Bioengineered Cell Therapies for Endocrine Dysfunction: Advancements and Clinical Prospects.
Drug-free in vitro activation combined with ADSCs-derived exosomes restores ovarian function of rats with premature ovarian insufficiency.
Overexpression of miR-20a-5p in mesenchymal stem cell derived-exosomes from systemic lupus erythematosus patients restored therapeutic effect and Treg immune regulation.
An engineered self-biomineralized oncolytic adenovirus induces effective antitumor immunity and synergizes with immune checkpoint blockade.
An updated review on the development of a nanomaterial-based field-effect transistor-type biosensors to detect exosomes for cancer diagnosis.

Neural Regen Res. 2025 May 01. 20(5): 1221-1235

Exosomes: the next-generation therapeutic platform for ischemic stroke.

Wenjing Yin, Hongyin Ma, Yang Qu, Jiaxin Ren, Yingying Sun, Zhen-Ni Guo, Yi Yang.

Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery. Therefore, there is an urgent need to develop new methods for the treatment of this condition. Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions. They have low immunogenicity, good stability, high delivery efficiency, and the ability to cross the blood-brain barrier. These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke. The rapid development of nanotechnology has advanced the application of engineered exosomes, which can effectively improve targeting ability, enhance therapeutic efficacy, and minimize the dosages needed. Advances in technology have also driven clinical translational research on exosomes. In this review, we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke, including their anti-inflammation, anti-apoptosis, autophagy-regulation, angiogenesis, neurogenesis, and glial scar formation reduction effects. However, it is worth noting that, despite their significant therapeutic potential, there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes. Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke. Ultimately, our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.

DOI: https://doi.org/10.4103/NRR.NRR-D-23-02051
Endocr Metab Immune Disord Drug Targets. 2024 Jul 23.

Bioengineered Cell Therapies for Endocrine Dysfunction: Advancements and Clinical Prospects.

Dilpreet Singh.



Keywords:  Bioengineered cell therapy; endocrine dysfunction; hormone replacement; regenerative medicine; stem cells; tissue engineering

DOI:  https://doi.org/10.2174/0118715303311209240709115156
J Ovarian Res. 2024 Jul 31. 17(1): 158

Drug-free in vitro activation combined with ADSCs-derived exosomes restores ovarian function of rats with premature ovarian insufficiency.

Qian Li, Zhiqiang Zhang, Wenxin Shi, Zhongkang Li, Yanlai Xiao, Jingkun Zhang, Xianghua Huang.

   BACKGROUND: Drug-free in vitro activation (IVA) is a new protocol to activate residual dormant follicles for fertility restoration in patients with premature ovarian insufficiency (POI). However, several deficiencies have reduced its clinical efficacy rate. Our previous studies have confirmed that the combination of adipose-derived stem cells (ADSCs) and drug-free IVA can improve the effectiveness of drug-free IVA and restore ovarian function of rats with POI. Increasing evidence has demonstrated that mesenchymal stem cell-derived exosomes have similar therapeutic effects as their source cells. Here, we performed a preclinical study to evaluate the therapeutic effects of ADSCs-derived exosomes (ADSCs-Exos) combined with drug-free IVA in the POI rats and the mechanism in restoring ovarian function.
RESULTS: In vivo, the effects of ADSCs-Exos were comparable to those of ADSCs, and the ADSCs-Exos combined with drug-free IVA was better than ADSCs-Exos alone therapy in promoting follicular development. Moreover, transplantation of ADSCs/ADSCs-Exos lead to up-regulation of BCL-2 expression and down-regulation of the expression of Bax and Cleaved Caspase-3, thus reducing the apoptosis of chemotherapy-induced follicle cells, and further promoting the development of the follicles and rescuing ovarian function in POI-damaged ovary. In vitro, ovarian fragmentation could activate follicular growth and development, and in combination with ADSCs-Exos could prevent the loss of follicles, promote follicular proliferation and inhibit apoptosis.
CONCLUSIONS: ADSCs-Exos combined drug-free IVA had remarkable therapeutic effects in restoring ovarian function of POI rats, and markedly promoted follicular development and inhibited apoptosis of ovarian cells in vitro. Our study confirmed that the combination therapy might be a promising and effective treatment for POI.

Keywords:  Adipose-derived stem cells; Apoptosis; Drug-free in vitro activation; Exosomes; In vitro ovarian culture; Premature ovarian insufficiency

DOI:  https://doi.org/10.1186/s13048-024-01475-4
Eur J Pharmacol. 2024 Jul 26. pii: S0014-2999(24)00551-X. [Epub ahead of print]979 176862

Overexpression of miR-20a-5p in mesenchymal stem cell derived-exosomes from systemic lupus erythematosus patients restored therapeutic effect and Treg immune regulation.

Juan Ji, Qian Liang, Qian He, Tian Chen, Guijuan Feng, Hua Guo, Yunan Wang, Yongxin Xu, Pengyu Chen, Chen Dong, Rui Zhao, Junling Yang, Xiaoqi Sha, Haixia Cao, Jing Li, Yunfei Xia, Mei Yang, Zhifeng Gu.

  We and other groups have documented that bone marrow-mesenchymal stem cells (BM-MSCs) from Systemic lupus erythematosus (SLE) patients demonstrated signs of senescence, including reduced ability of regulating Treg. Treg cell defects or Treg cell deficiency are regarded as significant factors in the progression of SLE. Exosomes, nanoscale vesicles, abound in molecular and genetic contents, play a critical role in intercellular communications. The purpose of this research is to investigate the mechanism of MSCs-exosomes regulating Tregs cells in SLE, further elucidate the mechanism of immune dysregulation of aging BM-MSCs, and provide theoretical basis and data support for new targets of SLE treatment. In the study, BM-MSCs and exosomes were isolated successfully. Exosomes could be up-taken by naïve CD4+T cells. MSCs-exosomes attenuated SLE clinical manifestation in vivo, but MSCs-exosomes from SLE patients were ineffective. MSCs-exosomes from SLE patients dysregulated Treg cells differentiation in vivo and in vitro. Exosomal miR-20a-5p contributed to the effect of MSCs-exosomes regulating Treg cells. Up-regulating the expression of miR-20a-5p in SLE MSCs-exosomes can restore their ability to promote Treg differentiation and treatment effect. This study further elucidated the role of in the immunomodulatory mechanism of BM-MSCs-exosomes and provided new ideas for the non-cellular autologous transplantation therapy of SLE.

Keywords:  Exosomes; Mesenchymal stem cells; MiRNA; SLE; Treg

DOI:  https://doi.org/10.1016/j.ejphar.2024.176862
Cancer Immunol Res. 2024 Aug 05.

An engineered self-biomineralized oncolytic adenovirus induces effective antitumor immunity and synergizes with immune checkpoint blockade.

Shibing Wang, Xue Yang, Ying-Yu Ma, Junjie Wu, Ketao Jin, Ruibo Zhao, Hai Zou, Xiaozhou Mou.

Oncolytic adenoviruses (oADV) are promising cancer treatment agents. However, in vivo hepatic sequestration and the host immunological response against the agents limit the therapeutic potential of oADVs. Herein, we present a combined, rational design method for improving oADV infection efficiency, immunogenicity, and treatment efficacy by self-biomineralization. We integrated the biomimetic nucleopeptide W6p into the capsid of oADV using reverse genetics, allowing calcium phosphate mineralization to be biologically induced on the surface of oADV under physiological conditions, resulting in a mineral exterior. This self-biomineralized, modified oADV (oADV-W6-CaP) enhanced infection efficiency and therapeutic efficacy in coxsackie and adenovirus receptor (CAR)-negative cancer cells while protecting them against neutralization by pre-existing neutralizing antibodies. In subcutaneous mouse tumor models, systemic injection of oADV-W6-CaP demonstrated improved antitumor effectiveness, which was associated with increased T-cell infiltration and CD8+ T-cell activation. In addition, the anticancer immune response elicited by oADV-W6-CaP was dependent on CD8+ T cells, which mediated long-term immunological memory and systemic antitumor immunity against the same tumor. Finally, the addition of PD-1 or CD47 inhibition boosted the anticancer effects of oADV-W6-CaP and raised the rate of complete tumor clearance in tumor-bearing animals. The self-biomineralized oADV shifted the suppressive tumor microenvironment from a "cold" state to a "hot" state and synergized with immune checkpoint blockade to exert outstanding tumoricidal effects, demonstrating promising potential for cancer immunotherapy.

DOI: https://doi.org/10.1158/2326-6066.CIR-23-0957
Talanta. 2024 Jul 22. pii: S0039-9140(24)00983-4. [Epub ahead of print]279 126604

An updated review on the development of a nanomaterial-based field-effect transistor-type biosensors to detect exosomes for cancer diagnosis.

Jeongyun An, Hyunjun Park, Minyoung Ju, Yeeun Woo, Yoshep Seo, Junhong Min, Taek Lee.

  Cancer, a life-threatening genetic disease caused by abnormalities in normal cell growth regulatory functions, poses a significant challenge that current medical technologies cannot fully overcome. The current desired breakthrough is to diagnose cancer as early as possible and increase survival rates through treatments tailored to the prognosis and appropriate follow-up. From a perspective that reflects this contemporary paradigm of cancer diagnostics, exosomes are emerging as promising biomarkers. Exosomes, serving as mobile biological information repositories of cancer cells, have been known to create a microtumor environment in surrounding cells, and significant insight into the clinical significance of cancer diagnosis targeting them has been reported. Therefore, there are growing interests in constructing a system that enables continuous screening with a focus on patient-friendly and flexible diagnosis, aiming to improve cancer screening rates through exosome detection. This review focuses on a proposed exosome-embedded biological information-detecting platform employing a field-effect transistor (FET)-based biosensor that leverages portability, cost-effectiveness, and rapidity to minimize the stages of sacrifice attributable to cancer. The FET-applied biosensing technique, stemming from variations in an electric field, is considered an early detection system, offering high sensitivity and a prompt response frequency for the qualitative and quantitative analysis of biomolecules. Hence, an in-depth discussion was conducted on the understanding of various exosome-based cancer biomarkers and the clinical significance of recent studies on FET-based biosensors applying them.

Keywords:  Biosensor; Cancer diagnosis; Exosomal biomarker; Field-effect transistor

DOI:  https://doi.org/10.1016/j.talanta.2024.126604