Culturing Mesenchymal Stem Cells for Regenerative Medicine

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Mesenchymal stem cells (MSCs) are multipotent adult stem cells that can differentiate into various cell types including bone, cartilage, fat, and muscle cells. They have shown immense promise in regenerative medicine for treating orthopedic injuries, autoimmune conditions, and neurodegenerative diseases. However, there is an ongoing debate about whether MSCs should be culture-expanded in labs before being used for treatments.

Stem Cell Medical Center, a regenerative medicine provider, advocates using expanded MSCs over non-expanded cells from umbilical cord tissue. They have been culturing MSCs for over 8 years and believe expanded cells, when done properly, are more potent.

Non-Expanded vs Expanded MSCs

Non-expanded MSCs are derived from donated whole umbilical cord tissue and placenta after healthy live births. They cannot be replicated further due to FDA regulations in the US. This usually yields 10-30 million MSCs which is a decent number but limited.

To obtain MSCs, the umbilical cord is dissected to extract Wharton’s jelly and the placenta’s capillaries. The cells are chemically separated and suspended in a solution like sodium lactate. They are then cryogenically frozen and shipped to treatment centers.

Many question whether frozen MSCs are still viable. However, experts ensure that freezing does not damage stem cells if thawed using precise timescales and temperature gradients. So it’s vital to ask providers about their thawing protocol.

The main drawback of using non-expanded cells is that the isolation process may traumatize them. They enter “survival mode” and secrete fewer therapeutic exosomes and cytokines.

In contrast, culture-expanding MSCs allow exponential growth of up to billions of daughter cells from one umbilical cord. The cells are replicated in controlled, optimal lab conditions with abundant nutrients to promote growth. Up to 3 rounds of culture preserves cell potency. We believe that going beyond to 7 expansion rounds leads to abnormal, weaker cells with reduced function. The ideal target expansion is 3 rounds.

Mechanism of Action: The Paracrine Effect

MSCs exert their effects via paracrine signaling. They can detect nearby cell types in the body and secrete a plethora of bioactive molecules like cytokines and exosomes that coordinate regenerative processes.

For example, MSCs will rush to sites of inflammation caused by an injury or autoimmune attack. They can stimulate new tissue growth, suppress inflammation, decrease fibrosis, and regulate immune cells based on factors they detect in that tissue.

Each exosome packed with specific cytokines and growth factors acts like a GPS-guided missile targeting areas needing repair. So MSCs don’t just randomly dump molecules. This highly targeted paracrine activity is why they successfully treat diverse conditions.

Cultured MSCs Grown in “Stem Cell Eden”

Expanded MSCs are replicated in optimized lab environments specifically designed to nourish and sustain them.

The stem cells are placed in a growth medium containing the precise nutrients, proteins, and substrates needed for that cell type to divide and proliferate. They grow in a sterile incubator with the ideal humidity, pH, and temperature.

This simulates the regenerative micro-environment stem cells experience in the body. The end result is robust daughter cells programmed to carry out repair processes via paracrine signaling.

In a way, culture expansion allows “farmed” MSCs grown in a controlled stem cell Eden to reach their full therapeutic potential.

Safety Concerns Around Cultured MSCs

A common objection is that lab-grown daughter cells might be less safe or potent compared to innate MSCs straight from umbilical tissue. However, research indicates otherwise:

  • Daughter MSCs are identical clones with the same surface proteins and genotype as parent stem cells. They retain phenotypic stability for up to 10 passages.
  • MSCs lack MHC-II surface receptors that trigger immune reactions. So allogeneic cultured MSCs aren’t rejected.
  • Animal studies found no abnormal cell growth or increased toxicity with culture-expanded MSCs even after extensive subculturing.
  • MSCs begin differentiating into various tissue cells after 8-12 months. The transient presence of donor cells causes no issues.
  • The body routinely clears millions of aged red blood and immune cells daily, so eliminating a small fraction of differentiated MSCs is easily managed.

In summary, controlled culture expansion generates more robust “super donor” MSCs without compromising safety or potency.

The Limited Shelf Life of MSCs

MSCs do lose some potency and decline in number after multiple divisions. This is more pronounced after the 10th passage.

Hayflick’s limit refers to the number of times a normal human cell can divide before it stops dividing. Specifically, most human cell types can only divide around 50-70 times before reaching cellular senescence. Senescence means the cell is no longer able to divide but remains alive and metabolically active. However, MSCs exhibit early senescence around passages 12-15.

Telomere shortening likely contributes to reduced cell division capacity. Regardless, only up to 6 passages are required to generate a clinically relevant MSC dosage.

Matched Donor MSCs for Certain Conditions

Younger MSCs from birth-associated tissues have a longer proliferative lifespan compared to adult-sourced MSCs. Umbilical cord MSCs may be preferable for genetic defects, while matched donor cells suit some autoimmune disorders.

For example, a patient’s own bone marrow-derived MSCs already reflect dysfunctional immune changes underlying autoimmunity. Using their cells could worsen the condition. Instead, matched MSCs from a close relative lacking the autoimmune tendency may be appropriate. The cells are still recognized as “self” and not rejected.

How Do MSCs Know What to Do?

The astounding ability of MSCs to detect their surrounding microenvironment and secrete tailored growth factors remains an intriguing area of research.

MSCs express various cell surface receptors to sample signals from nearby cells. Integrins, Toll-like receptors, and other receptor systems relay information to the intracellular matrix about local needs.

This intercellular crosstalk via paracrine signaling directs MSCs to release a specific blend of cytokines, chemokines, and exosomes. Through mechanisms still being unraveled, MSCs collect “intel” about tissue damage and deploy molecules to enact repairs.

Exosomes: MSC Messengers for Regeneration

Exosomes are a major paracrine effector of MSCs. These lipid vesicles encapsulate and transfer various bioactive molecules between cells. MSCs discharge large amounts of exosomes that travel to sites of injury and inflammation.

Exosomes carry payloads with different cytokines and microRNAs that reduce inflammation, stimulate new vessel growth, decrease scarring, neutralize toxins, and provide other therapeutic effects.

Researchers found just 400,000 MSCs could produce around 80 billion exosomes in 12 weeks!

Some clinics offer exosome therapy without MSCs. But exosomes lack direction without MSCs guiding them to the right locations. Their clinical effectiveness as solo treatments remains questionable. Since MSCs naturally secrete abundant exosomes, administering additional exogenous exosomes may provide no extra benefit. MSCs are the commanders that deploy exosomes like tiny guided missiles. Removing MSCs makes exosomes less targeted.

Are Cultured MSCs Just a Profit-Driven Fad?

Critics argue that expanded MSCs are a ploy by for-profit clinics to increase profits rather than benefit patients. If non-expanded MSCs worked well, companies would simply use the cheaper umbilical cord tissue option.

They contend natural MSCs straight from the source are best, while cultured cells are artificial profit-driven products.

However, the high costs of building cGMP labs and navigating complex regulations are the main barriers to providing culture-expanded MSCs. The cells themselves are not inherently more expensive or difficult to produce.  

In fact, switching to easier non-expanded cells would slash production costs. But cultured MSCs offer more flexibility in generating cell numbers needed for therapies. Umbilical cords also have very limited harvest yields.

Many established researchers maintain culturing does not change key markers or effectiveness if done properly. The controversy stems more from commercialization concerns rather than science.

Canada and other countries permitted cultured MSC treatments in the past but later restricted their use after lobbying by the pharmaceutical industry and medical groups. The superior outcomes threatened conventional revenue streams.

Money and politics have played a role in impeding expanded MSC therapies, despite strong clinical evidence for their safety and efficacy over non-expanded cells.

The Takeaway on Culture-Expanded MSCs

In summary, properly expanded MSCs generate robust cells that retain full regenerative capacity based on current research. Controlled replication in optimal lab conditions maximizes the paracrine potency of MSCs.

Non-expanded MSCs still offer benefits and are suitable when the cell numbers needed are lower. But their isolation can impair function. Well-characterized culture-expanded MSCs are preferable for many patients.

More clinical studies directly comparing expanded vs non-expanded MSCs will provide greater clarity. But the existing data makes a persuasive case for the advantages of supplementing innate MSCs through careful culture-expansion protocols.

At Stem Cell Medical Center, we strive to provide the most scientifically-advanced and ethically-sourced stem cell treatments available. Our clinical team has decades of experience safely administering cultured mesenchymal stem cells to patients suffering from a wide range of conditions.

We believe controlled culture expansion of MSCs using precise protocols generates more potent cells without compromising safety or viability. This allows us to help more patients by producing the ideal stem cell dosages needed for regenerative therapies. If you or a loved one are suffering from an orthopedic injury, autoimmune disorder, or another condition, expanded MSCs could help where other treatments have failed. Contact Stem Cell Medical Center today to schedule a consultation with one of our highly-trained regenerative medicine experts.