Dear Editor,
First of all we would like to thank Dr. Shapiro and colleagues for their clear and exhaustive answers to the points raised. We agree that many aspects of the use of stem cells in the treatment of osteoarthritis (OA) still need to be clearly defined, and likely lots of preclinical and clinical trials will be needed to draw any reliable conclusion. Given the various protocols and administrative methods currently in use, designing a “flawless” randomized controlled trial (RCT) might seem utopian, but researchers must find a compromise between “scientific needs” and real-world feasibility. To this purpose we recognize the usefulness of pilot studies, whose aim is to identify optimal strategies in order to minimize bias before starting a larger trial. In this particular case, we felt that the risk of having 2 “unmatched” sets of knees was high, and that the addition of Platelet-poor plasma introduced an additional confounding factor. Not only must appropriate randomization methods be used, but the mixing of biological products must also be avoided. Simple solutions, such as increasing the amount of bone marrow harvested to obtain more bone marrow concentrate (BMC) for intra-articular injection, can compensate these issues, and are necessary to guarantee the reliability of results. In hindsight, it is always easier to find something that you would have done differently: we truly appreciate the honesty of Dr. Shapiro and colleagues and we thank them again for sharing their experience, which has been most helpful for us and all researchers involved in the use of biologic therapies for OA treatment.
Berardo Di Matteo
Filippo Vandenbulcke
Elizaveta Kon
Istituto Clinico Humanitas, Rozzano, Milan, Italy