‘Exosomes’: The Hype, the Chasm, and Beyond

Gartner's Hype Cycle (GHC) is a cornerstone framework for tracking the progression of emerging technologies through five distinct stages (Figure 1). The term ‘cycle, ’ derived from ‘circle, ’ suggests a process that conceptually returns to its starting point, evoking repetition, or renewal. This makes GHC a misnomer: it rather models a strictly linear progression of technological maturation that will end in a binary outcome (flourish or perish). Since its inception in 1995, Gartner has published over 130 such analyses annually, offering a structured lens to evaluate, and, to a certain extent predict, technology maturation and adoption. It complements other frameworks, such as Gartner's Impact Radar, Geoffrey Moore's Technology Adoption Life Cycle, and NASA's Technology Readiness Levels, each providing different perspective on innovation dynamics (Moore 1999, Sadin et al. 1989, Gartner Inc). These tools are primarily meant to guide timely and informed decisions of business strategists on when and if to place their bets on promising and ‘hot’ technologies, to ensure adequate return on investment. However, they have also been extensively used by scientists and science administrators, particularly in grant applications like the European Innovation Council (EIC) schemes, where demonstrating feasibility and impact is critical. Although science-driven innovation plays an important role in building up the hype and driving technologies through the cycle, the application of the GHC by scientists is not always fully appropriate, often overlooking many ‘moving parts’ that are essential for the successful transformation of innovation into a marketable product. Analysts themselves are not free of biases. The heavy reliance on GHC and similar frameworks without consideration of other contextual cues, akin to the overuse of journal impact factors, risks oversimplifying complex technological and scientific progress, prioritizing visibility and hype over substantive evidence and long-term impact. This can lead to skewed priorities, where technologies and authors are judged more on perceived prestige than down-to-earth outcomes. As The Economist critiques, GHC lacks deep historical anchoring or granular analysis of drivers and obstacles, requiring cautious interpretation (The Economist 2024). The same article notes that many, if not most, blockbuster technologies didn't travel through a GHC. Although imperfect and somewhat speculative, GHC can be useful for benchmarking of emerging scientific and technology novelties. With such premises, we cared to make a reflection on the applications and applicability of GHC on Extracellular Vesicles (EV) technologies tackled in the Commentary by Salehi et al. , ‘Extracellular Vesicles and The Gartner Hype Cycle’ (Salehi et al. 2025). Why EV Remain Off Gartner's Radars? Salehi et al. , propose a long historical EV timeline, dating it back to early 1940s. EVs, as membrane-bound particles released by cells were first characterized in the 1980s (with earlier observations of platelet-derived particles in the 1960s) (Johnstone et al. 1987, Pan and Johnstone 1983). They have certainly come a long way to get acknowledged by vast scientific community to hold transformative potential across healthcare (Zarovni et al. 2021). Yet, EV have not appeared on the official GHC or Gartner's Impact Radar, both prioritizing the technologies with 0–10-year market timelines. Several factors may explain this absence. Foremost, EV are often viewed as a field of fundamental research, too niche-confined and still grappling with methodological challenges and fundamental biology, for clinical use. The continuous stream of publications re-examining the isolation options, semantics and key EV properties and characteristics, although often cited by EV researchers as a positive landmark, is keeping the field in the discovery phase. This positions EV as pre-commercial, lacking the maturity to trigger Gartner's focus. In fact, Gartner does not consider fundamental science, but ‘notices’ the burgeoning technologies, as they transition from a niche area of study, towards a recognition as platforms for mainstream market demands, either untapped or brand-new. Moreover, diversity of potential EV applications complicates their categorization. Unlike lipid nanoparticles (LNPs) or mRNA platforms, which gained traction during COVID-induced biotech bubble, EV span across diagnostics, therapeutics, and consumer products. This breadth diffuses their market narrative, making it harder to pinpoint a singular ‘trigger‘ for GHC benchmarking. Alternatively, we can suppose that EV have been subsumed under broader categories like cell/gene therapies (CGTs) or genomic medicine, tracked in Gartner's Life Sciences Hype Cycles since 2020. In 2025 GHC (Gartner Inc), CGTs remain in the Trough of Disillusionment, with 5–10 year to-plateau, while genomic tools ascend the Slope of Enlightenment (2–5 years). Finally, Gartner's emphasis on digital technologies—AI, smart diagnostics, and data platforms—further overshadows ‘wet’ biotech like EV. For instance, AI-driven drug discovery dominated Gartner's 2025 priorities. The Hype Surge: Icarus Takes Flight. In the Commentary, the authors rightly define GHC as a ‘useful lens for examining the evolution of enthusiasm, scepticism, and eventual maturation in the field. ’ Indeed, the GHC tracks a societal perception of technology's readiness rather than actual engineering capability; it is our behavioral patterns—such as excitement over the prompt use of novel technologies and a ‘herd behavior’—that fuel a contagious hype. Moderate hype attracts funding, talents, and attention; excessive hype inflates expectations, leading to disillusionment when delivery falters. When the hype bubble bursts, the interest of investors and potential users will rapidly decline; higher and hastier the hype, steeper and deeper is this fall. This dynamic is central to understanding EVs’ trajectory. While we tend to agree with the key stones marking the early EV history aligned by Salehi et al. , we also add some complementary landmarks and metrics, and propose a slightly different view of the timing and pace of transition of EVs along the GHC-like path. The Inflated Expectations peaked around 2015–2018, with the EV publicized as the next big thing in diagnostics first (e. g. for cancer liquid biopsies), shifting overwhelmingly, almost cannibalizing the diagnostic hype, to regenerative medicine (e. g. , stem cell-derived EVs for tissue repair), drug delivery (e. g. , for RNA therapeutics), and vaccine platforms. Publications surged from ∼1, 000 in 2015 to ∼5, 000 in 2020, reflecting a fivefold increase in research output (Van Delen et al. 2024). The NIH's Extracellular RNA communication program catalyzed funding, with over 100 M allocated to EV-related projects by 2020. Over 100 EU research and innovation projects having to do with EVs were publicly funded by 2021, and over 50 companies were advancing EV claims globally. Some companies attracted significant venture and corporate capital (Zipkin 2020): Codiak Biosciences (168 M raised by 2017 and first filed for IPO in 2018), Evox Therapeutics (169 M raised by the end of 2021), ExoPharm (IPO at Australian Stock Exchange in 2018), while Exosome Diagnostics got acquired by Bio-Techne (250 M plus up to 325 M in potential milestones in 2018). In 2018 the first high-profile EV deals included Roche's partnership with PureTech and Lonza's equity stake in Exosomics. Clinical momentum concurred: of ∼500 EV-related trials registered by September 2025, ∼100+ were listed by October 20207. COVID accelerated the hype around EVs, with stem cell-derived EVs tested for acute respiratory distress syndrome (ARDS) Phase II studies, as well exosome-based vaccines (Clinical Trials Register: NCT04493242) while Codiak was heading toward IND filings for exoSTING and exoIL-12 in cancer, coming out later on (2021), all showcasing EV therapeutic potential. Instrument providers adapted platforms for EV analysis, with nanoflow cytometry (NanoFCM), super-resolution microscopy (ONI), and interferometric spectrometry (NanoView) gaining traction. This surge amplified EVs’ perceived disruptive potential and expectations, while also priming—the fall. The Trough: Icarus Falls The field did not have to wait for long to re-evaluate what appeared to be success stories. First evidence of under-delivery came soon, revealing the issues with reported performance of first generation of applications and products. Some providers of research grade EV technologies thrived, but no big businesses decollated relying on serving exclusively EV research market. First released products (in particular the diagnostic ones) hit the market but did not reach wide adoption, failing to meet post-acquisition milestones for their sponsors. While early investors were able to capitalize on EV hype, many had to bear significant losses. It became evident that business models and technology offerings of EV startups needed re-assessment. Internal programs and timelines of some blockbuster EV startups were cut or remodeled, some assets changed hands after the first important business drops (Codiak Bioscience bankruptcy in 2023 and latest, September 2025, Bio-Techne's divestiture of Exosome Diagnostics to MDxHealth SA). It also became evident that the perpetuated under-design of EV trials, lacking proper control arms and sufficient enrollment, impeded any well founded demonstration of efficacy and, to a lesser degree safety, and therefore conclusion about EV therapeutic potential. Salehi et al. highlight this lack of robust clinical data and manufacture stability issues as major hurdles holding back the EV translation, that along with immature market demand and sustained lack of adequate funding, created a ‘Catch-22 situation’. EV production suffered from insufficient capacity and inappropriate quality metrics. The surge in surrogate parameters for vesicle profiling/characterization could not circumvent the need to define mechanism of action (MoA). The lack of common terminology criteria and delay in adoption of regulatory compliant guidelines exacerbated the variety and under-reporting of trials1 (Moore 1999, Pan and Johnstone 1983) that made impossible to correlate adverse events or efficacy of the EV treatments to manufacturing parameters or EV dosage. Finally, safety alerts against using unauthorized and potentially dangerous EV based treatments have been released by ISEV and the FDA, echoing similar issues that have been raised years ago for stem cells or gene therapies (U. S. Food and Drug Administration, Fujita et al. 2024). The hype bubble burst, and volatile focus of external stakeholders—beyond the EV ‘fans’—shifted to other biotech trends with a clearer biology, manufacturing and developmental strategies. Indeed, some uncontrollable market shifts accelerated EVs slide into the trough of disillusionment. The meteoric rise of LNPs and mRNA platforms during COVID somewhat diverted investment, with mRNA funding peaking at 5. 2 billion in 2021 while EV venture capital dropped ∼40% by 2022. Advances in other diagnostic modalities, such as high-resolution MRI for prostate cancer, eroded EV-based liquid biopsies’ competitive edge. Similar to other pre-deployment stage technologies, the EV field faced a tattered landscape of capital deficits and dissatisfied investors. Fast forwarding to 2025, raising capital from institutional investors or securing big pharma partnerships has proven challenging, with successful deals yielding upfront payments at a minuscule fraction of the multimillion-dollar checks secured during EVs’ ‘golden age’. Rising from ashes: Icarus Reascends However, the saying is that ‘every cloud has a silver lining’. The EV technology trajectory, slower than anticipated, persists along the linear GHC path without falling off. Having sunk into the Trough, EVs now show early signs of climbing the slope of enlightenment. This GHC phase learns from initial launches, setbacks and imperfect solutions to drive more realistic progress, illuminating EVs’ unique strengths and identifying lead practical applications. Second-generation applications leverage clarified technical requirements and benefits, addressing clinical challenges not only alternatively, but also complementarily to other modalities. We cannot put in the same baskets areas such as diagnostics and therapy that travel at different pace, but progress is being made, alongside: regenerative dermatology is flourishing via co-development with major brands and celebrity endorsements, riding consumer wellness trends. This can be a double-edged sword for EVs social acceptance. Unlike commonly thought, the manufacturing and regulatory claims for cosmetics, especially in some geographies, are not trivial. In EU human stem cells derivatives are still not allowed in cosmetic products, significantly limiting outreach of EV-based products. Scrutiny is needed to determine whether EVs are the key API that drive efficacy in these products or merely pixie dust sprinkled to capitalize on the hype wave, as their functional contribution often lacks rigorous validation. Still, regulatory clearance in dermatology could catalyze topical therapeutics. In last couple of years, we witnessed EV diagnostics resurge: Mursla Bio's EvoLiver test earned FDA Breakthrough device designation (April 2025) for liver cancer surveillance. Mercy BioAnalytics’ 59 M Series B (September 2025) should advance and extend cancer tests pipeline. At the same time therapeutics lag somewhat behind, with most EVs in Phase I, and few in Phase 2/3 (Pan and Johnstone 1983). ExoBiologics’ EVENEW trial, EMA-authorized for bronchopulmonary dysplasia, advances to Phase II, with interim data due by the end of 2025. Despite hundreds of EV trials registered by 2025, only a few are robustly designed, and even fewer report results. The weakened position of the EV therapeutics space is also evident in the focus erosion and strategic ‘diversification’ pursued by many companies in the sector. Facing capital constrains for advancing standalone therapeutic pipelines, most EV therapeutic companies have diversified their operations to include CRO/CDMO services or launched specialized subsidiaries to ensure financial viability, often by offering EVs as row ingredients for buyers in regenerative dermatology and unregulated markets. Therefore, the risk of falling back into the cycle, instead of progressing ahead, is still high in this first recovery phase. The authors of the Commentary (Moore 1999) provided a nice summary of challenges and possible solutions from the perspective of EV research community as innovation driver, prioritizing rigor and transparency in experimental design and reporting, as well as adherence to internationally formulated guidelines. Indeed, to recover the credibility and appeal, EV innovators must place rigor over hype. The innovation in academia as well as in the startup community, needs to be responsible. The EV community continues to grow, attracting new talents and navigated experts. EV persistently permeate innovation forums. This turnover hold risks of recycled claims and approaches, sometimes advanced by new entries, that can trap stakeholders in outdated loops. Reliable oversight and education must counter exaggerations, channeling methodological scale-up into viable clinical and commercial pipelines. Besides ISEV's Task Forces already highlighted by Salehi et al. , cross-society groups (ISEV-ELBS, ISEV-ISCT), and translation, regulatory and advocacy committee can and should drive this shift not only in narrative but in approaches and execution. Transparent reporting of experimental and manufacturing protocols with confirmed reproducibility, is vital for EV space survival. Editors should boldly refuse the studies conducted on inappropriate models, single biological replicates or two-mice groups. ISEV has advanced standardization through MISEV and EV-TRACK, but these guidelines have not been massively adopted and, in line with their scope, have not addressed all critical parameters for drug development. To advance the excellence science into valuable product, the guidelines made by-researchers-for-researchers, need to be plugged in pre-validated regulatory and CMC blueprints that are developed and validated in the similar sectors (e. g. CGT). As shown by Selahi et al. ’s Commentary, the adoption of EVs features and technologies beyond the research is acknowledged, but, to our understanding, the adoption beyond the EV niche versus the mainstream spread, has not yet been considered. Crossing the chasm. According to GHC, a technology exits the trough of disillusionment when adopted by a small (5%) fraction of its potential customer base, but mainstream acceptance hinges on bridging this gap. Real world adoption operates at different pace than a hype, and not all adopters are the same. This is explained by another cycle that is often used to monitor the diffusion of emerging technologies—The Adoption Cycle (Moore 1999). GHC aligns with the adoption cycle (Figure 2). Crossing the chasm signals ascent to the plateau of productivity, yielding mainstream traction and return on investment. At that point the technology deployment can propel along the S shaped curve. 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