Dr. Weeks’ Comment: Stem cells are valuable only because they deliver exosomes. In and of themselves, they offer no value. Think of the stem cell as the bank envelop which itself is without value but is able to deliver the real value, the cash within. If you are considering stem cells, think again. Read below For more info on the revolution in revitalization, exosomes, call and schedule a consult with Dr. Weeks 360-341-2330.
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Cell Mol Bioeng. 2020 Feb; 13(1): 1–16. Published online 2019 Dec 23. doi: 10.1007/s12195-019-00607-x
Engineering of Exosomes to Target Cancer Metastasis
Zhenjiang Zhang,#Jenna A. Dombroski,# and Michael R. King
Extracellular vesicles (EVs) were first described by Trams et al. in 1981 as cell-secreted particles that carried membrane-bound enzymes, and could be taken up by recipient cells.112 The authors keenly predicted that EVs could represent an important pathway to transfer information between cells and might be developed to package and deliver therapeutic molecules like structurally similar liposomes. However, initially EVs were more widely regarded as “garbage bags” for disposal of undesired cellular components.116 A subset of extracellular vesicles in the 30–150 nm range, which are released from cells upon fusion of an intermediate endocytic compartment called the multivesicular body (MVB) with the plasma membrane, were later defined as exosomes.93 Exosomes were subsequently found to be specialized for intercellular signaling by carrying proteins, nucleic acids, lipids and metabolic cargo from source cells to neighboring recipient cells or even to distant organs.75
Exosomes facilitate effective intercellular communication that can regulate cellular functions such as proliferation, apoptosis and migration.40 Mounting studies support the understanding of exosomes as key players in tumor growth.40,72 In fact, cancer cells have been found to secrete more exosomes than noncancerous cells.6 Over the last decade, exosomes shed by cancer cells have been found to facilitate metastasis, which accounts for over 90% of cancer-related deaths.101,123,126,127,141 Metastasis occurs when a cancer cell derived from a primary tumor intravasates into the bloodstream in the form of a circulating tumor cell, which has the potential to grow into a secondary tumor following extravasation.114Evidence has supported that exosomes play a critical role in several steps in the metastatic process.141 As a result, exosomes have become an increasingly important research target for the prevention of metastasis.127 Anti-metastatic treatments that have attracted intensive research efforts include immunotherapy such as chimeric antigen receptor T (CAR T) cells or TRAIL-coated leukocytes as well as stem cell and virotherapy.78,87,113,121
Exosomes have been pursued as a delivery vehicle for a variety of therapeutics for targeted treatment.7,11,69,73,104,132 Compared to artificial nanoscale vehicles, exosomes possess a number of advantages that can be exploited. For one, exosomes naturally deliver their membrane and cytoplasm components by fusing with the target cell membrane.7 Exogenous therapeutics can thus be encapsulated in exosomes and delivered in a hitchhiking manner. In addition, exosomes, particularly those collected from patient tissues or blood, possess low immunogenicity and thus intrinsic long-term circulatory capability, and excellent biocompatibility.64 Several studies also suggest that exosomes secreted by specific cell types exhibit a very specific cell tropism, supporting highly targeted cargo delivery.
Our growing understanding of the biology of exosomes and experience in engineering exosomes for diagnostic or therapeutic purposes have provided promising potential for the treatment of tumor metastases.13,22,68 In this review, we discuss the recent advances concerning the engineering of exosomes to target metastasis, with a focus on the methods of exosome isolation and engineering, and therapeutic effects of engineered exosomes for antimetastatic therapy. We will only briefly introduce the biogenesis, structure, and contents of exosomes, and their roles in cancer, as several existing review articles have covered these topics….
Exosomes are specialized intercellular messengers that alter the functional state of their target cells by delivering cargo such as proteins and nucleic acids from their parental cells. The role of exosomes in cancer including metastasis has been intensively investigated. Understanding of their properties and activities have provided a solid foundation to engineer exosomes for the targeting of metastasis, which could significantly increase survival among cancer patients. After a decade of research, many engineered exosome engineering methods including those for isolation and cargo incorporation have proven to be successful for modifying exosomes with desirable diagnostic and therapeutic functionalities. Application of engineered exosomes to target metastasis have yielded encouraging results that support further development toward clinical practice.