PUR Biologics, LLC, a biotech company focused on biologics and devices for musculoskeletal conditions, had its proprietary cell culture tested by University of Wisconsin to see if stem cells cultured in substrates with PUR’s extracellular matrix were able to increasingly proliferate and maintain or enhance their multilineage differentiation capacity.
The answer was yes with a surprising breakthrough.
Work led by Dr. Wan-Ju Li in the Department of Orthopedics and Rehabilitation and the University of Wisconsin-Madison demonstrated—for the first time—the ability of a naturally secreted human extracellular matrix (hECM) to not only support the proliferation of mesenchymal stem cells (MSCs), but to also upregulate the genes associated with hyaline cartilage formation, according to Ryan Fernan, CEO of PUR Biologics.
Further, this work showed that MSCs treated with hECM had increased chondrogenic potential, or increased potential to form cartilage, than untreated MSCs.
“We found that PURmatrX was able to maintain MSC phenotype before differentiation induction and able to differentiate into chondrocytes expressing collagen type 2, a maker for hyaline cartilage, ” Fernan said. “The findings suggest we can use PURmatrX to culture stem cells for treatment of orthopedic diseases and be used to treat joints, bone, tendon and intervertebral disc repair.”
PUR and Histogen Joint Venture
Manufactured by PUR’s joint venture partner Histogen, Inc., the extracellular matrix (PURmatrX) utilized in this research is produced through a proprietary novel technology process which triggers the de-differentiation of fibroblast cells into multipotent stem cells through low oxygen and special culture conditions. “This results in a hECM that is embryonic-like without utilizing embryonic stem cells, and that has potential benefit in a number of orthopedic applications, ” Fernan said.
“Dr. Li’s work demonstrates how PUR’s materials maintain the perfect environment for your body’s own cells to naturally and effectively heal itself, potentially providing a vitally needed solution to the millions suffering from cartilage complications, ” Fernan said.
About the Research
The concept of mesenchymal stem cells revived and supported an explosion of interest in using these uniquely therapeutic cells for various regenerative medicine applications. It has now been several decades since Dr. Arnold Caplan defined these cells. It’s been about a decade since the first MSC-based stem cell product came to market in orthopedics.
And, today, the field is crowded with various MSC-based autologous or homologous products—all with widely varying rates of efficacy.
In fact, it is becoming increasingly difficult to define precisely what an MSC is—in part because of it’s plasticity, in part because of the extraordinary wide range of anatomical environments it is directed to and in part because, now, researchers have identified more than 60 different surface protein markers which define what precisely a MSC can or cannot do in a given therapeutic application.
MSCs were originally identified in bone marrow and later detected in many other tissues. Currently, no cloning based on single surface marker is capable of isolating cells that satisfy the minimal criteria of MSCs from various tissue environments.
So markers are increasingly critical to defining the stemness or, put another way, therapeutic potential of MSCs. Many MSC surface markers or markers which define some aspect of stemness have been brought forward so far. We recently counted more than 60.
But the reality is that there is a large difference in the expression of these surface markers in various sources of MSCs.
So, when these University of Wisconsin researchers established that their MSCs had specific cell surface markers, CD73+, CD90+, CD105+, and CD45−, it was highly significant. These cell markers are known to have a greater therapeutic capacity than the MSC population as a whole. Importantly, this latest research has shown that by culturing MSCs with hECM the number of cells with these markers increases exponentially.
“The main limitation of MSC therapies is the inability to grow a sufficient number of cells without changing their characteristics, ” said Dr. Li. “We have found that hECM both increases the proliferate of these cells and primes them to become chondrocytes, which has the potential to be hugely impactful in the treatment of various cartilage disorders.”
In addition, MSCs treated with hECM were shown to produce more collagen type 2, the primary collagen in articular cartilage, and collagen type 10, the primary collagen in the calcified cartilage layer. At the same time, treatment with hECM reduced the production of collagen type 1 which is distributed in fibrocartilage. This suggests that hECM may be well suited in the induction of hyaline cartilage formation.
The results of this research support previous studies in full thickness osteochondral defects in rat, rabbit and goat models, where mature hyaline cartilage was formed after implantation of hECM.
The paper entitled “Effects of Human Fibroblast-Derived Extracellular Matrix on Mesenchymal Stem Cells” is currently published in the online edition of Stem Cell Reviews and Reports, available at http://link.springer.com/journal/12015/onlineFirst/page/1.
Fernan acknowledges that there are other groups using ECM derived from different cell types, but says this study is unique because “we have demonstrated that the PURmatrX used in this study is able to drive stem cells to become hyaline cartilage not hypertrophic cartilage that eventually turns into bone.”
