The Must-Ask Questions a Harvard MD Wants You to Ask Before Stem Cell Treatment

There is a level of transparency every patient should expect when considering a form of regenerative therapy, where a physician not only understands the power of what regenerative medicine is capable of but also doesn’t dismiss its current limitations. Whether you’re considering stem cells, exosomes, or platelet-rich plasma, science has a lot of catching up to do. Yet with billions on the table, the industry isn’t slowing down to find out.

The global regenerative medicine market is projected to grow from $58.40 billion this year to $360.84 billion by 2034, according to industry predictions. More than 1,500 businesses promote stem cell treatments across the United States, according to research. All the while, a 2024 study found that a significant percentage of stem cell clinic websites disclosed neither the risks of treatment nor the limited evidence behind it, leaving patients misled and often taken advantage of.

Dr. David Karli, founder of the Karli Health Institute in Miami, has spent two decades treating orthopedic injuries with various regenerative procedures, including stem cells, platelet-rich plasma, and exosomes, and he doesn’t pretend the field is full of good actors.

“There’s just so much misinformation, and there are so many claims out there,” Karli tells Muscle & Fitness. “The elephant in the room is that there’s lots of money to be made, and you have people in it for the right reasons and for the wrong. The consumer needs to be able to weed out the difference between the two.”

Tests to Run Before Determining Which Protocol Is Right

Karli says the process should start with a consultation built around a specific goal as opposed to aimlessly picking a treatment off a menu.

“Are you here for regenerative medicine? Are you here for longevity and wellness? Or are you here for both?” Karli begins.

Then he relies on imaging to pin down exactly the level of damage present before choosing a protocol. He drills deep to investigate, for example, what stage of arthritis it is. Whether it’s one compartment or all three compartments. Whether there’s an associated meniscal tear and what the patient’s bone health underneath the cartilage looks like. He says, these all affect how to apply the cell therapy and where.

From there, Karli’s clinic runs bloodwork focusing on a few key markers, like vitamin D, hs-CRP to quantify systemic inflammation, HbA1c, and hormone levels, to catch any deficiencies or imbalances that need addressing before moving forward with a protocol. However, he doesn’t deny how much is still unsettled. “There are some [biomarkers] that empirically make sense in terms of tracking, but the science is still early, and we’re also learning which ones are important and may have predictive value.”

How Do You Know You’re the Right Candidate

Not every joint is a good candidate, and not every treatment has an equally predictable outcome.

“Someone who has grade-two knee arthritis is a perfect candidate, because they’re not so early in the process, but they’re not so far gone that it’s a long shot either,” Karli says. Grade three or four disease [bone-on-bone arthritis] can still respond, he adds, but the odds shift. “The more severe the disease, the less predictable our likelihood of success becomes.”

Which protocol fits also depends on whether a patient is using their own cells or a donor product, which is a decision with its own tradeoffs. “If it’s done in the right circumstances, using your own cells is a relatively low-risk procedure,” Karli says. “If you’re using a donor model, however, they are foreign and not invisible to the immune system and are good at evading the immune system.” This is why the questions you ask must be taken seriously before treatment.

Additionally, using your own cells, caps how many sites can be treated at once. He says the limit is no more than two, which rules the approach out for anyone hoping to address several joints in a single visit.

He adds that in the United States, patient counseling is critical so they know that these are FDA-unapproved therapies. Donor cells haven’t been vetted like a normal drug would through a prolonged FDA process. “We anecdotally have seen patients in offshore models do this for 20 years,” he explained. “And by and large, we’re not seeing a lot of serious adverse events and deaths and really awful things, but they’re also not reporting their adverse events, so we really don’t truly know the long-term safety and efficacy.”

Karli is careful not to oversell what any of this can do. “We’re not at a point with regenerative medicine yet where we can reverse disease,” he says, adding that the value is rather in improving function and quality of life for his patients. “We can manage disease effectively in most cases, not all, but most. We’re not reversing it yet, but we’re working toward it because ultimately we want a solution where we can undo the degenerative process and reverse it back to normal.”

Ranking the Evidence

Karli measures success by duration. “To make this a cost-effective value to a patient spending lots of money, we’ve got to capture the duration of lasting relief.” Karli’s clinic has spent years measuring protocols against two-year outcomes across thousands of treatments, feeding an AI model that predicts individual odds of success before a patient ever gets an injection. “I want to be able to say you have an 86.7% chance of getting 70% relief at two years,” Karli says. “That allows us to counsel powerfully to help the patient make a truly informed decision whether they should or shouldn’t move forward.”

Going beyond stem cells, there are a couple more options to consider. For simpler soft-tissue injuries like tendonitis, Karli says correctly dosed PRP performs well on its own. Inside a joint, he leans toward stem cells for their lasting power. “With PRP, you’ve got to repeat them. They just don’t hold that long,” he says.

Exosomes, the cell-free “messenger” therapies marketed as an alternative to stem cells, leave him intrigued but unconvinced that the science has caught up. “The way I like to explain exosomes to the consumer is a message in a bottle,” he says. The open question, he says, is whether a lab can reliably reproduce the same signal a stem cell would release naturally inside an arthritic joint. “Is it apples to apples? The answer is we don’t know yet.”

Must-Ask Questions of the Doctor

Karli wants people to have the awareness and agency to separate a legitimate clinic from a room with a centrifuge and a marketing budget. He recommends that you prepare a list of questions to make sure you’re in good hands.

“Number one, is it legal?” he starts. “Does the physician understand the law? Is this a side hustle for their practice, or is this what they do full time? How many patients have you treated? Are you collecting outcomes? Do you know your dose? How many platelets, how many white blood cells, how many monocytes?” He points to dosing specifically as a place where patients get shortchanged without knowing it. “If someone comes to me and says, ‘I tried PRP,’ I say, ‘Did your doctor know the dose?,’ and if they say, ‘No,’ well, then how do I know if it worked or not?”

For donor stem cells specifically, he adds a second round of questions. Since Florida passed a law effective July 1, 2025, licensed physicians now may perform stem cell therapy that the FDA hasn’t approved, as long as it’s used for orthopedics, wound care, or pain management, and falls within that physician’s scope of practice.

The law states, however, that cells must be sourced from FDA-registered facilities certified by one of a specific list of accrediting bodies (the National Marrow Donor Program, the American Association of Tissue Banks, among others), processed under current Good Manufacturing Practices, and accompanied by a post-thaw viability report before use.

You should ask: “Did they screen the donor? Did they check for communicable diseases? Did they check for bacterial contaminants? Did they do a viability analysis? Can you show me the report?”

Karli says the industry standard for viability, the percentage of cells still alive at injection, is 70%, a bar he considers too low. “I think that is nowhere near acceptable,” he says. His own clinic retests every shipment before it’s used, something the law doesn’t require. He adds that a well-cultured stem cell that’s well-handled and managed through the freezing and thawing process should be able to achieve over 90% viability. “In these offshore models, if you’re not measuring viability, you have no idea what you’re getting,” he cautions.

He also tells patients to ask whether cells are being culture-expanded in a lab or simply concentrated and reinjected the same day, especially for anyone being offered treatment in several joints in a single visit. “If they’re not culture expanding, then there’s no evidence to support that whatsoever,” he says of that approach. “I wouldn’t recommend it.”

Last, he says, ask about the injection itself. “Are you guiding it with ultrasound or X-ray? Are you trained to be precise and safe with the implantation?”

“If you just start with these questions, you’re way ahead of the game,” he makes the point.