Exosomes. take off of Stem Cell



CAP-2003 is comprised of exosomes isolated from the company’s proprietary cardiosphere-derived cells (CDCs). It is being developed as a next-generation therapeutic platform in regenerative medicine and as a vehicle to deliver therapies to cells in the human body.

Exosomes are nano-sized, membrane-enclosed vesicles, or “bubbles,” that are secreted by cells and contain bioactive molecules, including proteins, RNAs and microRNAs. They act as messengers to regulate the functions of neighboring cells. Pre-clinical research has shown that exogenously-administered exosomes can direct or, in some cases, re-direct cellular activity, supporting their therapeutic potential. Their size, ease of crossing cell membranes and ability to communicate in native cellular language make them an exciting class of potential therapeutic agents.

Because of their unique capacities, researchers are increasingly viewing exosomes as vehicles to deliver gene and other therapies to cells in the human body. CAP-2003 offers a unique potential to serve not only as a vehicle for delivering the therapies but also as a therapeutic. Pre-clinical studies have indicated CAP-2003 has potential as a treatment for diseases of inflammation and fibrosis, including Duchenne muscular dystrophy, a fatal genetic disease.

CAP-2003 is immunomodulatory, meaning it can balance the immune system to potentially restore cell damage. The exosomes also have the capacity to reduce inflammation or swelling, which damages cells, and they can reduce cell death and decrease fibrosis or scarring.

Cedars-Sinai Medical Center has granted Capricor worldwide rights to its CDC exosome technology under an exclusive license agreement.



LOS ANGELES, Aug. 21, 2018 (GLOBE NEWSWIRE) -- At the Gordon Research Conference on Extracellular Vesicles in Newry, Maine, Capricor Therapeutics (NASDAQ: CAPR) presented research findings on the mechanism of action and the immunomodulatory capacities of CAP-2003, the company’s investigational therapy comprised of proprietary extracellular vesicles, including exosomes, which are derived from cardiosphere-derived cells (CDC-EVs). Capricor is developing CAP-2003 as a therapeutic platform for treating diseases involving inflammation and fibrosis.

The Gordon Research Conference on Extracellular Vesicles is focused on cutting-edge research on the biogenesis, molecular composition, functions, physio-pathological roles and potential clinical applications of extracellular vesicles. Gordon Research Conferences are a group of prestigious international scientific conferences that are at the forefront of research in the biological, chemical and physical sciences and their related technologies.

“The pre-clinical studies presented at the Gordon Research Conference further elucidate Capricor’s progress in developing this exciting new class of therapeutics, the exosomes which comprise our investigational therapy, CAP-2003,” said Linda Marbán, Ph.D., Capricor chief executive officer. “The studies further demonstrate that exosomes may be the active pharmaceutical ingredient (API) in CAP-1002, our cell therapy product, because these extracellular vesicles serve as cellular-messengers, altering function and physiology to balance inflammation so that cellular repair can be facilitated.”

In the first study, Capricor compared CAP-2003 with exosomes made from mesenchymal stem cells (MSCs). The research found that CAP-2003 contains a unique cocktail of microRNAs, non-coding RNAs and proteins that drive greater immunomodulation, suggesting that CAP-2003 may be a more efficacious product candidate in diseases of inflammation and fibrosis.

This study also showed that CAP-2003 polarizes macrophages – a type of white blood cells involved in removing cellular debris and in tissue repair – to elicit anti-inflammatory and pro-regenerative responses. In addition, the study found that CAP-2003 has an immunomodulatory effect on T-cells, modifying the immune response of this critical component of the immune system. Researchers concluded that this study supports the use of CAP-2003 for the potential treatment of inflammatory indications.

An abstract from the second study reported that in a mouse model of Duchenne muscular dystrophy, CAP-2003 produced improvements that are similar to those attributed to CAP-1002, Capricor’s cell therapy product. The findings suggest that the exosomes that make up CAP-2003 mediate the CDCs’ mechanism of action. Capricor researchers also tested in vitro uptake of CDC-EVs by different cell types and found that CDC-EVs are taken up by immune cells with little uptake by fibroblasts and epithelial cells. This finding sheds further light on the mechanism of action of CDC-EVs in modulating inflammation and stimulating tissue repair.

Capricor is now conducting HOPE-2, a Phase II, randomized, double-blind, placebo-controlled study of repeat doses of CAP-1002 delivered intravenously. The study is enrolled in approximately 84 boys and young men in advanced stages of Duchenne muscular dystrophy. For more information on HOPE-2, please visit www.HOPE2Trial.com.

The posters presented at the Gordon Conference will be available on the Events & Presentations section of Capricor's website.

About Duchenne Muscular Dystrophy

Duchenne muscular dystrophy is a devastating genetic disorder that causes muscle degeneration and leads to death, generally before the age of 30, most commonly from heart failure. It occurs in one in every 3,600 live male births across all races, cultures and countries. Duchenne muscular dystrophy afflicts approximately 200,000 boys and young men around the world. Treatment options are limited, and there is no cure.

About CAP-1002

CAP-1002 is comprised of allogeneic cardiosphere-derived cells, or CDCs, a unique population of cells that contains cardiac progenitor cells. CAP-1002 has been shown to exert potent immunomodulatory activity and stimulate cellular regeneration. CDCs have been the subject of over 100 peer-reviewed scientific publications and have been administered to approximately 140 human subjects across several clinical trials.

About CAP-2003

CAP-2003 is being developed as a next-generation therapeutic platform in regenerative medicine. CAP-2003 is comprised of nano-sized extracellular vesicles, including exosomes and microvesicles, derived from human CDCs, which exert anti-inflammatory, pro-angiogenic, anti-apoptotic, and anti-fibrotic effects. CAP-2003 contains several characteristic lipids, proteins, and RNA molecules (e.g., microRNAs). They act as messengers to regulate the functions of neighboring cells. Pre-clinical research has shown that exogenously-administered extracellular vesicles can direct or, in some cases, re-direct cellular activity, supporting their therapeutic potential. Their size, ease of crossing cell membranes and ability to communicate in native cellular language make them an exciting class of potential therapeutic agents.

About Capricor Therapeutics

Capricor Therapeutics, Inc. (NASDAQ:CAPR) is a clinical-stage biotechnology company focused on the discovery, development and commercialization of first-in-class biological therapeutics for the treatment of rare disorders. Capricor’s lead candidate, CAP-1002, is an allogeneic cell therapy that is currently in clinical development for the treatment of Duchenne muscular dystrophy. Capricor has also established itself as one of the leading companies investigating the field of extracellular vesicles and is exploring the potential of CAP-2003, a cell-free, exosome-based candidate, to treat a variety of disorders. For more information, please visit www.capricor.com.

Keep up with Capricor on social media: www.facebook.com/capricortherapeutics, www.instagram.com/capricortherapeutics/ and https://twitter.com/capricor.

Cautionary Note Regarding Forward-Looking Statements

Statements in this press release regarding the efficacy, safety, and intended utilization of Capricor's product candidates; the initiation, conduct, size, timing and results of discovery efforts and clinical trials; the pace of enrollment of clinical trials; plans regarding regulatory filings, future research and clinical trials; regulatory developments involving products, including the ability to obtain regulatory approvals or otherwise bring products to market; plans regarding current and future collaborative activities and the ownership of commercial rights; scope, duration, validity and enforceability of intellectual property rights; future royalty streams, expectations with respect to the expected use of proceeds from the recently completed offerings and the anticipated effects of the offerings, and any other statements about Capricor's management team's future expectations, beliefs, goals, plans or prospects constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Any statements that are not statements of historical fact (including statements containing the words "believes," "plans," "could," "anticipates," "expects," "estimates," "should," "target," "will," "would" and similar expressions) should also be considered to be forward-looking statements. There are a number of important factors that could cause actual results or events to differ materially from those indicated by such forward-looking statements. More information about these and other risks that may impact Capricor's business is set forth in Capricor's Annual Report on Form 10-K for the year ended December 31, 2017 as filed with the Securities and Exchange Commission on March 22, 2018, in its Registration Statement on Form S-3, as filed with the Securities and Exchange Commission on September 28, 2015, together with the prospectus included therein and prospectus supplements thereto and in its Quarterly Report on Form 10-Q for the quarter ended June 30, 2018, as filed with the Securities and Exchange Commission on August 13, 2018. All forward-looking statements in this press release are based on information available to Capricor as of the date hereof, and Capricor assumes no obligation to update these forward-looking statements.

CAP-1002 is an Investigational New Drug and is not approved for any indications. CAP-2003 has not yet been approved for clinical investigation.


Why did Texas A&M ink big deal with stem cell clinic firm Celltex on exosomes?


The recent news that Texas A&M University has inked a full-blown deal with the direct-to-consumer stem cell clinic firm Celltex struck me as an unusual development.

Recently we’ve seen more universities exploring the use of stem cells outside of the traditional FDA clinical trial process that is fundamentally based on an investigational new drug application (IND). Some institutions apparently have even potentially started teaming up with clinics for patient treatments muddying the waters out there. However, in the case of Celltex and Texas A&M my guess would be that they are going to work on their joint project within the FDA trial system. We’ll see what more we learn over time.Texas A&M Celltex

A reminder is in order here that a half-dozen or so years ago Celltex got an FDA warning letter that led the firm to start doing stem cell transplants across the border in Mexico. A main issue at hand at that point was the use of an adipose stem cell product that the FDA called a biological drug, but that lacked full FDA pre-market approval. With a new Texas state law that on some levels is friendly to stem cell firms that seem to operate outside the traditional FDA clinical trial framework, I’ve been wondering: might Celltex aim to bring more of its efforts back into its home state? This news regarding working with Texas A&M suggests a potential affirmative answer.

What exactly is this new deal between Texas A&M and Celltex?

It appears to be focused on testing the idea that mesenchymal stem cells (MSC) or more specifically their exosomes (little subcellular packages by which cells can share resources or influence each other’s behavior) could help with Alzheimer’s Disease (AD). Could exosomes reduce inflammation in the diseased brain in a meaningful, safe way? If so, would that help AD? The Texas A&M researchers have some notable initial data on these exosomes in an animal model, but I’m not clear on how directly relevant it is to the proposed work as I need to do more reading.

There aren’t a lot of specific details of the agreement between the Texas A&M Institute for Regenerative Medicine and Celltex in the press release either. An article by Todd Ackerman in the Houston Chronicle provides some more answers. In the deal, Texas A&M gets funding from the company for the use of the technology:

“Celltex will pay Texas A&M $2.4 million to acquire the technology and ultimately bring it to market.”
Celltex gets intellectual property and potentially boosted credibility from Texas A&M, which could be worth way more than $2.4 million to the company. Again, the firm ran into FDA issues a half-dozen or so years ago, but Ackerman’s piece quotes the company saying that things are different now:

“The company is currently compliant with the FDA, said David Eller, Celltex’s CEO.”
Ackerman’s article doesn’t provide context for objectively evaluating Celltex’s statement of compliance. We need to learn more about what this means. The FDA decides what’s compliant and what isn’t, and we don’t know if FDA recently told Celltex that they are compliant and for what specifically.

Moving forward, will this team effort with Texas A&M need an IND to be compliant prior to going into human studies? It seems so from my perspective and I’d imagine the Texas A&M researchers will work with the FDA to build an IND application. Why would an IND most likely be needed here?

If there is infusion of adipose MSCs into patients for AD, that sounds like it would potentially involve both more than minimal manipulation and non-homologous use designations coming into play, both possible regulatory triggers for requiring an IND and pre-market approval by the FDA. However, it’s hard to know without more details.

What if it’s just the exosomes? Even though stem cells themselves may not be used here ultimately in patients in a trial if the work gets to that point, my understanding is that exosomes would be considered a biological drug. In fact, to make adipose MSC exosomes for infusion one would need to first isolate fat stem cells (which the FDA has said makes the cells a drug) and then isolate exosomes from them. To me that sounds like a lot of production steps if one would claim minimal manipulation. If the MSCs are grown in a lab prior to isolation of exosomes that could also contribute to making the product a drug. For these reasons, the team may be planning an IND for this joint effort as they approach the point of a future Phase I trial.

More broadly, I wondered about a possible Celltex IND a few years back in my 2015 yearly stem cell predictions, but that prediction was specifically related to their own MSC transplants directly to consumers. On that front, I don’t know if they have or plan to get an IND, or if they hope to resume those particular clinical operations within Texas rather than just Mexico, but from the Chronicle again, Celltex does seem to be aiming to get more clinical work going in Texas:

“Under a new state law that sanctions experimental stem cell therapy in Texas, Celltex hopes to again begin providing its stem cells to doctors and hospitals in the state, said Eller. Celltex, he said, is waiting on rules being drawn up by the Texas Health and Human Services Commission as part of the law, passed by the 2017 Legislature.”
If Celltex resumes MSC injections in Texas without an IND (to be clear this would likely be independent of the work with Texas A&M, and again for all I know Celltex could have an IND for their MSCs), could there end up being an interesting collision of state and federal authorities as this develops? This is going to be an important story to follow on many levels.


Exosomes — beyond stem cells for restorative therapy in stroke and neurological injur


Exosomes — beyond stem cells for restorative therapy in stroke and neurological injury
Zheng Gang Zhang, Benjamin Buller & Michael Chopp
Nature Reviews Neurologyvolume 15, pages193–203 (2019) | Download Citation


Stroke is a leading cause of disability worldwide, and brain injuries devastate patients and their families, but currently no drugs on the market promote neurological recovery. Limited spontaneous recovery of function as a result of brain remodelling after stroke or injury does occur, and cell-based therapies have been used to promote these endogenous processes. Increasing evidence is demonstrating that the positive effects of such cell-based therapy are mediated by exosomes released from the administered cells and that the microRNA cargo in these exosomes is largely responsible for the therapeutic effects. This evidence raises the possibility that isolated exosomes could be used alone as a neurorestorative therapy and that these exosomes could be tailored to maximize clinical benefit. The potential of exosomes as a therapy for brain disorders is therefore being actively investigated. In this Review, we discuss the current knowledge of exosomes and advances in our knowledge of their effects on endogenous neurovascular remodelling events. We also consider the opportunities for exosome-based approaches to therapeutic amplification of brain repair and improvement of recovery after stroke, traumatic brain injury and other diseases in which neurorestoration could be a viable treatment strategy.

Key points

Exosomes are involved in many aspects of normal brain physiology and facilitate communication between brain cells and between the brain and the periphery.

Increasing evidence suggests that exosomes from mesenchymal stromal cells (MSCs) mediate the beneficial effects of cell therapy for stroke and traumatic brain injury (TBI).

The effects of MSC-derived exosomes alone have the potential to improve neurological outcomes in animal models of stroke, TBI and other neurological diseases.

Of the cargo in exosomes, microRNA (miRNA) is of prime importance in mediating the therapeutic effects.

Compared with naive MSC-derived exosomes, engineered MSC-derived exosomes that contain selected miRNA have more potent therapeutic effects in stroke and TBIs.


Pioneer Founding member
I haven't heard anything recently about Celltex's plans. I hope they are able to start treating patients in Texas once again. It's very difficult for those who are ill to have to go to Cancun for treatment. Full speed ahead Celltex!


Barbara, I am not sure why anyone needs to go to Mexico now, most is done in USA using cord blood PRP and same with Wharton's Gell and other treatments using
Placenta and Umbilica cord. Many clinics doctors are giving shots from umbilical cord/placenta fluids on a cheaper basis while some give through IV.


Pioneer Founding member
The reason patients are going offshore is that the clinics can legally expand their cells. Dr. Centeno for instance has a clinic in Grand Cayman. Many MS patients I know go to Celltex in Cancun as well as Dr Riordan's clinic in Panama. It wouldn't make much sense to go offshore if a patient lives in the U.S. if the same kind of treatment could be obtained here and for close to the same price. Unfortunately, that is not the case.